4,867 research outputs found

    The Collective Dynamics of Smoking in a Large Social Network

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    Based on repeated surveys of 12,067 closely interconnected people between 1971 and 2000, examines the extent to which smoking spreads socially and to which groups of smokers quit together, as well as trends in the number and social centrality of smokers

    A Teacher in the Living Room? Educational Media for Babies, Toddlers, and Preschoolers

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    Examines available research, and arguments by proponents and critics, of electronic educational media use by young children. Examines educational claims in marketing and provides recommendations for developing research and product standards

    Friendship and Natural Selection

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    More than any other species, humans form social ties to individuals who are neither kin nor mates, and these ties tend to be with similar people. Here, we show that this similarity extends to genotypes. Across the whole genome, friends' genotypes at the SNP level tend to be positively correlated (homophilic); however, certain genotypes are negatively correlated (heterophilic). A focused gene set analysis suggests that some of the overall correlation can be explained by specific systems; for example, an olfactory gene set is homophilic and an immune system gene set is heterophilic. Finally, homophilic genotypes exhibit significantly higher measures of positive selection, suggesting that, on average, they may yield a synergistic fitness advantage that has been helping to drive recent human evolution

    Identification and characterization of novel enzymes in mitochondrial and cytosolic nucleotide metabolism

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    Nucleotides need to be synthesized within the cells since there are no carrier proteins for them in the cell membrane and their negatively charged phosphate groups prevent diffusion across the membrane. There are two main pathways for nucleotide synthesis: the de novo pathway and the salvage pathway. Both pathways involve several phosphorylation steps that result in the synthesis of the nucleoside triphosphates. The enzymes that catalyze the conversion of the nucleoside monophosphates to their corresponding diphosphates are called nucleoside monophosphate kinases (NMPKs). A subgroup of NMPKs is the adenylate kinase (AK) family that catalyzes the nucleotide phosphoryl exchange reaction between adenosine monophosphate (AMP) and adenosine triphosphate (ATP) and thus regulates adenine nucleotide ratios in different intracellular compartments. The previously characterized AK5 was shown to be the second domain of a holoenzyme that we characterized in this thesis. The full-length AK5 exists in two similar transcript variants that differ in a 26 amino acid fragment in the N-terminus. AK5 is cytosolic or both cytosolic and nuclear depending on the transcript variant and it was shown to have two separate functional domains with the same AK activity. Both the full-length AK5 and its first domain phosphorylate AMP, deoxyadenosine monophosphate (dAMP), cytidine monophosphate (CMP) and deoxycytidine monophosphate (dCMP) with ATP or guanosine triphosphate (GTP) as phosphate donors. Human AK4 was previously characterized as a mitochondrial enzyme but no enzymatic activity was confirmed. In this thesis, AK4 was further characterized and we were able to detect enzymatic activity. AK4 phosphorylates AMP, dAMP, CMP and dCMP with ATP or GTP as phosphate donors and kinetic studies showed that AMP is the preferred substrate. The mitochondrial import sequence of AK4 was found to be located within the first N-terminal 11 amino acid residues, very close to the ATP-binding site of the enzyme. Import analysis suggested that the mitochondrial import sequence is not cleaved and thus AK4 retains its activity upon entering the mitochondria. In an attempt to complete the picture of the family of human AK isozymes, we characterized the previously identified AK7 and furthermore, we identified and characterized a novel AK which we named AK8. AK8 proved to have two functional domains. AK7, full-length AK8 and the two domains of AK8, all phosphorylate AMP, dAMP, CMP and dCMP with ATP as phosphate donor but also AMP, CMP and dCMP with GTP as phosphate donor. Kinetic studies showed that both enzymes are more efficient in AMP phosphorylation compared with the major cytosolic isoform AK1. Both AK7 and AK8 are located in the cytosol. In our last study, we used previously generated and characterized CEM cells, resistant to the nucleoside analog 9-β-D-arabinofuranosylguanine (araG). By using microarrays, several genes with different biological functions were found to be down- or up-regulated. The main cytosolic AK isoform, AK1 was shown to be up-regulated, a finding that was further investigated both at the gene expression and the protein expression level. The study suggested that increased AK activity might contribute to araG resistance
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