A preparation of decapitated Drosophila melanogaster has been used for direct application of drugs to the nerve cord. Serotonin, dopamine, and octopamine stimulate locomotion and grooming, showing distinguishable effects that often are potentiated by addition of the vertebrate monoamine oxidase-inhibitor hydrazaline. Many of the hydrazaline-induced effects are sexually dimorphic, with males showing greater responses than females. Behaviors similar to those induced by dopamine can be induced by application of the vertebrate dopamine D2-like receptor agonist quinpirole, whose effects are also sexually dimorphic. In contrast, vertebrate D2-like and D1-like dopamine antagonists result in akinesic states, and D1-like agonists selectively stimulate grooming. These data indicate that Drosophila nerve cord amine receptors are coupled to ref lexive behaviors similar to those stimulated by brain dopamine receptors in vertebrates.In both vertebrates and invertebrates, the basic neural oscillators controlling reflex behaviors and locomotion are contained within the spinal cord, or the nerve cord in the case of invertebrates (reviewed in refs. 1-6). Several nonhuman vertebrates show both locomotion and reflex scratching behaviors in response to irritants even after the spinal cord is cut. Similarly, decapitated insects show a basal level of spontaneous grooming as well as a normal grooming response when a sensory bristle is stimulated by gentle mechanical contact (5, 6). Studies in both Drosophila and larger insects show that the grooming response consists of a stereotyped series of leg, wing, and body movements that result in removal of debris from the legs and body of the fly (6-8).Many of these behaviors can be stimulated by application of biogenic amines. Injection of L-DOPA and 5-HTP, the precursors for dopamine͞noradrenaline and serotonin, respectively, can initiate walking motor patterns in spinal cats (9-11) and rabbits (12), although a more recent study shows that adrenergic agents are the most effective (13). Similarly, in partly dissected preparations of moth and locust, addition of dopamine or octopamine to the thoracic ganglia leads to stimulation of flight motor and stepping oscillators (14-16), and in cockroaches, dopamine can stimulate an escape response (17). These applications of exogenous biogenic amines likely mimic the roles of amines and͞or noradrenaline provided to the nerve or spinal cord from the brain by descending projections that are found in both vertebrates and insects (18,19). The invertebrate nerve cord differs from the higher vertebrate spinal cord in that the nerve cord contains aminergic cells bodies (20)(21)(22)(23). Presumably these cell bodies provide localized sources of amines to regions of the nerve cord neuropil that are not accessed by the descending aminergic projections.In vertebrates and invertebrates, dopamine and other amines act through families of G protein-linked seven transmembrane receptors (reviewed in refs. 24-26). Stimulation or inhibition of vertebrate dopamine...

Levels of job satisfaction, occupational commitment and intent to stay reported by nurses in this study can be improved. Suggested strategies for improvement are: increasing salaries, decreasing workloads, modifying task structure, cultivating work passion and creating more professional opportunity for nurses' personal growth development and promotion. Enhancing nurses' job satisfaction and occupational commitment are vital to improve nurses' intent to stay and for strategies to address the nursing shortage.

Allelic variation of gene expression is common in humans, and is of interest because of its potential contribution to variation in heritable traits. To identify human genes with allelic expression differences, we genotype DNA and examine mRNA isolated from the white blood cells of 12 unrelated individuals using oligonucleotide arrays containing 8406 exonic SNPs. Of the exonic SNPs, 1983, located in 1389 genes, are both expressed in the white blood cells and heterozygous in at least one of the 12 individuals, and thus can be examined for differential allelic expression. Of the 1389 genes, 731 (53%) show allele expression differences in at least one individual. To gain insight into the regulatory mechanisms governing allelic expression differences, we analyze a set of 60 genes containing exonic SNPs that are heterozygous in three or more samples, and for which all heterozygotes display differential expression. We find three patterns of allelic expression, suggesting different underlying regulatory mechanisms. Exonic SNPs in three of the 60 genes are monoallelically expressed in the human white blood cells, and when examined in families show expression of only the maternal copy, consistent with regulation by imprinting. Approximately one-third of the genes have the same allele expressed more highly in all heterozygotes, suggesting that their regulation is predominantly influenced by cis-elements in strong linkage disequilibrium with the assayed exonic SNP. The remaining two-thirds of the genes have different alleles expressed more highly in different heterozygotes, suggesting that their expression differences are influenced by factors not in strong linkage disequilibrium with the assayed exonic SNP.

BackgroundSmoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status.MethodsMicroarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite.ResultsMicroarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53).ConclusionWe have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression.