Biomedical subjects

George K Acquaah-Mensah

Publications and source records attributed to George K Acquaah-Mensah.

3 recordsLinked to original sources

PubMed2006

Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum.

BACKGROUND: Lowered sensitivity to the effects of ethanol increases the risk of developing alcoholism. Inbred mouse strains have been useful for the study of the genetic basis of various drug addiction-related phenotypes. Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice differentially express a number of genes thought to be implicated in sensitivity to the effects of ethanol. Concomitantly, there is evidence for a mediating role of cAMP/PKA/CREB signalling in aspects of alcoholism modelled in animals. In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined. RESULTS: A training dataset for Machine Learning (ML) and Exploratory Data Analyses (EDA) was generated from promoter region sequences of a set of genes known to be targets of CREB transcription regulation and a set of genes whose transcription regulations are potentially CREB-independent. For each promoter sequence, a vector of size 132, with elements characterizing nucleotide composition features was generated. Genes whose expressions have been previously determined to be increased in ILS or ISS cerebella were identified, and their CREB regulation status predicted using the ML scheme C4.5. The C4.5 learning scheme was used because, of four ML schemes evaluated, it had the lowest predicted error rate. On an independent evaluation set of 21 genes of known CREB regulation status, C4.5 correctly classified 81% of instances with F-measures of 0.87 and 0.67 respectively for the CREB-regulated and CREB-independent classes. Additionally, six out of eight genes previously determined by two independent microarray platforms to be up-regulated in the ILS or ISS cerebellum were predicted by C4.5 to be transcriptionally regulated by CREB. Furthermore, 64% and 52% of a cross-section of other up-regulated cerebellar genes in ILS and ISS mice, respectively, were deemed to be CREB-regulated. CONCLUSION: These observations collectively suggest that ethanol sensitivity, as it relates to the cerebellum, may be associated with CREB transcription activity.

Alcoholism↗

PubMed2006

Predicting the subcellular localization of human proteins using machine learning and exploratory data analysis.

Identifying the subcellular localization of proteins is particularly helpful in the functional annotation of gene products. In this study, we use Machine Learning and Exploratory Data Analysis (EDA) techniques to examine and characterize amino acid sequences of human proteins localized in nine cellular compartments. A dataset of 3,749 protein sequences representing human proteins was extracted from the SWISS-PROT database. Feature vectors were created to capture specific amino acid sequence characteristics. Relative to a Support Vector Machine, a Multi-layer Perceptron, and a Naive Bayes classifier, the C4.5 Decision Tree algorithm was the most consistent performer across all nine compartments in reliably predicting the subcellular localization of proteins based on their amino acid sequences (average Precision=0.88; average Sensitivity=0.86). Furthermore, EDA graphics characterized essential features of proteins in each compartment. As examples, proteins localized on the plasma membrane had higher proportions of hydrophobic amino acids; cytoplasmic proteins had higher proportions of neutral amino acids; and mitochondrial proteins had higher proportions of neutral amino acids and lower proportions of polar amino acids. These data showed that the C4.5 classifier and EDA tools can be effective for characterizing and predicting the subcellular localization of human proteins based on their amino acid sequences.

Algorithms↗

PubMed2002

In utero ethanol suppresses cerebellar activator protein-1 and nuclear factor-kappa B transcriptional activation in a rat fetal alcohol syndrome model.

A model of fetal alcohol syndrome was used to investigate prenatal ethanol effects on cerebellar transcription factors. Pregnant Sprague-Dawley rats were divided into three treatment groups: ethanol-exposed (E), calorically matched pair-fed (PF), and freely fed ad libitum (AL) groups. Ethanol exposure was stopped 2 days before parturition. The DNA binding in neonatal cerebella of the redox-sensitive transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) were determined by electrophoretic mobility shift assays. On the first postnatal day (PD1), there was decreased activation of these transcription factors in the E group relative to the control groups. The PD1 transcriptional effects were reversed as the neonate underwent development without further ethanol exposure. Western blot studies showed no corresponding decreases in protein amounts of both AP-1 and NF-kappa B components on PD1. Postnatal glutathione levels and catalase activity, as measures of oxidative stress hypothesized to be a probable cause of the transcriptional effects, showed no statistically significant effects attributable to ethanol. Examination of prenatal cerebella on embryonic day 20 (EM20), a time during ethanol exposure, showed DNA-binding trends similar to those of PD1. EM20 Western blot studies showed decreases in the levels of the active form of glycogen synthase kinase-3 (GSK-3). GSK-3 inhibition was reversed by PD1. Blocking of GSK-3 activity with gestational dietary lithium diminished both AP-1 and NF-kappa B DNA binding. Thus, prenatal ethanol exposure has the effect of diminishing pro-survival transcriptional activation, an effect possibly mediated by changes in GSK-3 activity.

Animals↗