Three dopamine pathways induce aversive odor memories with different stability

Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory.     

Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results.     

Modification of skeletal S-1 with fluorescein isothiocyanate

1. Pyridoxal-5'-phosphate (PLP), a marker of primary amines, bound covalently to S-1 in an approximate ratio of 1:1. PLP was localized within the tryptic 25,000 mol. wt fragment. 2. Fluorescein isothiocyanate (FITC), which is known to bind covalently to primary amino groups located at nucleotide binding sites, readily bound to S-1 in a 2:1 ratio. FITC was localized within the 20,000 and 50,000 mol. wt tryptic peptides, in a ratio of 1:1 in each one. 3. These results are consistent with the existence of nucleotide binding sites on myosin different from those of the catalytic sites.     

Analysis of yeast populations during alcoholic fermentation: a six year follow-up study

Wine yeasts were isolated from fermenting Garnatxa and Xarel.lo musts fermented in a newly built and operated winery between 1995 and 2000. The species of non-Saccharomyces yeasts and the Saccharomyces cerevisiae strains were identified by ribosomal DNA and mitochondrial DNA RFLP analysis respectively. Non-Saccharomyces yeasts, particularly Hanseniaspora uvarum and Candida stellata, dominated the first stages of fermentation. However Saccharomyces cerevisiae was present at the beginning of the fermentation and was the main yeast in the musts in one vintage (1999). In all the cases, S. cerevisiae took over the process in the middle and final stages of fermentation. The analysis of the S. cerevisiae strains showed that indigenous strains competed with commercial strains inoculated in other fermentation tanks of the cellar. The continuous use of commercial yeasts reduced the diversity and importance of the indigenous S. cerevisiae strains.     

The fliA gene encoding sigma 28 in Yersinia enterocolitica.

Yersinia enterocolitica is an enterobacterium responsible for gastrointestinal syndromes. Its pathogenicity depends on the presence of the 70-kb pYV plasmid, which directs Yop secretion. The Yop secretion machinery, consisting of the YscA-U and LcrD proteins, presents some structural similarity with the flagellum assembly machinery characterized in other bacteria. Flagellum assembly requires sigma 28, an alternative sigma factor. The region upstream of the lcrD gene resembles promoters recognized by sigma 28, suggesting that the similarity between Yop secretion and flagellum assembly could extend to their regulation. The chromosome of Y. enterocolitica also contains pathogenicity determinants such as myfA, which encodes the Myf antigen subunit. The promoter region of myfA also resembles promoters recognized by sigma 28. In an attempt to clarify the role of sigma 28 in the expression of lcrD, myfA, and flagellar genes, we cloned, sequenced, and mutagenized the fliA gene encoding the sigma 28 homolog in Y. enterocolitica. As is the case in other bacteria, fliA was required for motility. However, it was involved neither in fibrilla synthesis nor in Yop secretion. The fliA mutant allowed us to monitor the role of motility in pathogenesis. At least in the mouse model, motility seemed not to be required for Y. enterocolitica pathogenesis.