Functional Role Of Pathways Research Articles

Impact of normalization and filtering on linkage analysis of gene expression data

Using the Problem 1 data set made available for Genetic Analysis Workshop 15, we assessed sensitivity of linkage results to a correlation-based feature extraction method as well as to different normalization procedures applied to the raw Affymetrix gene expression microarray data. The impact of these procedures on heritability estimates and on expression quantitative trait loci are investigated. The filtering algorithm we propose in this paper ranks genes based on the total absolute correlation of each gene with all other genes on the array and has the potential to extract features that may play role in functional pathways and gene networks. Our results showed that the normalization and filtering algorithms can have a profound influence on genetic analysis of gene expression data.

Neurotransmitters, drugs and brain function

This book was written by members of the Pharmacology Department at University College London and was based on the undergraduate teaching courses provided by the Department. This basis is evident in the refreshingly unstuffy style of the book, and it is often easy to hear the lecturer speaking on the topic as one reads about it. This style does give rise to some unusual colloquialisms, for example NMDA receptors are described as coming in four main flavours. Professor Webster has done an excellent job with editing this book as well as writing approximately half of it, so that the chapters are all logically organized and there is not inappropriate overlap between them. The first section comprises a good overview of neurotransmitters, neuronal circuitry, regulation of neuronal activity and ion channels, neurotransmitter release and receptor structure and function. The second part describes drug action at receptors and pharmacokinetics, and then details specific neurotransmitters including information on agonists, antagonists, and their role in functional pathways. There are some surprising omissions from this section, for example there is no mention of mutations of acetylcholine receptors underlying autosomal dominant nocturnal frontal lobe epilepsy. It is also indicated that no excitatory amino acid receptor antagonists have been tested clinically as antiepileptic drugs – the results of a clinical trial of D-CPP-ene were published in 1993. The section on GABA does not mention the clinically used reuptake blocker, tiagabine. The third section describes neurotransmitters in health and disease and includes a useful overview of pharmacological targets, and then the range of neurological and psychiatric conditions and their pharmacological treatments. This section would have benefited from clinical input. The part on the clinical and electroencephalographic features of epilepsy, for example, is dated and the description of the affects of antiepileptic drugs in animal models does not include medications that have been licensed since 1990. In conclusion, this book gives a good overview and foundation of the topics covered in a very readable format that will be well suited for undergraduates studying Neurosciences. In fast moving areas of Neuroscience, however, books are soon out of date, and readers may need to supplement this book with a Medline search of specific areas that they are interested in.

Functional roles of monoaminergic pathways to sympathetic preganglionic neurons.

Despite considerable progress in mapping the central monoaminergic pathways to sympathetic preganglionic neurons in the spinal cord, the respective functional roles of these pathways have not been resolved. Evidence for both excitation and inhibition has been advanced for each of the three monoamines, serotonin, norepinephrine, and epinephrine. Our previous studies on spinal sympathetic pathways to sympathetic preganglionic neurons support the prevailing opinion that serotonin pathways are inhibitory but did not satisfactorily resolve the functional role of the norepinephrine pathways. However, more recent studies showing that intraspinally evoked sympathetic discharges were rapidly and markedly enhanced by phosphodiesterase inhibitors and that this effect was prevented by clonidine have led to formulation of a coherent hypothesis which accommodates much of the conflicting evidence regarding norepinephrine. In addition, evidence for the role of the epinephrine pathways has been obtained by using a selective inhibitor of epinephrine synthesis. The results of these recent studies complement our previous results and suggest that the excitability of sympathetic preganglionic neurons is regulated by excitatory norepinephrine pathways and inhibitory epinephrine pathways that activate or suppress adenylate cyclase to control intraneuronal levels of cyclic AMP.