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Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n = 171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced (IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN) enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles) versus slow metabolizers (PM/IM or PM/PM) were investigated through random effects models, with 'study' as the random factor, and Cox regression models, adjusting for confounders. Rapid metabolizers had higher endoxifen levels than slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8 versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels, demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a median follow-up of 12 years, rapid metabolizers with prior history of breast neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Trials investigating tamoxifen dose adjustments based on the woman's hormonal context and CYP2D6 genotype are warranted.

Debaryomyces hansenii is one of the yeast species most frequently isolated from cheese and salty foods, however little is known about the phenotypic and molecular variability of its strains. In order to explore the possibilities of a large study on its biodiversity, some D. hansenii strains were selectively isolated from pecorino cheese sampled in ten different Italian regions. All isolates were identified as D. hansenii on the basis of conventional and molecular taxonomic analysis. The D1/D2 domain sequences of the 26S-rDNA did not show any variation, confirming the extreme homogeneity of this species. PCR-duplex-RAPD banding patterns analyzed with PCoA showed interesting clustering related to the geographic areas of isolation, although some overlapping between strains derived from different districts could be observed. A FTIR (Fourier Transform Infrared Spectroscopy) metabolomic fingerprint produced groupings weakly related to those observed with RAPD and less associated with the isolation locales. The discriminatory power of metabolomic fingerprint was able to discriminate strains otherwise considered identical. This preliminary study showed that, in spite of the homogeneity at the 26S-rDNA level, the D. hansenii strains exhibit high molecular and metabolomic variability somehow linked to the places of isolation. Further studies will be necessary to better investigate on the link between terroir and strain variability, as well as on the relation between genotypic and metabolomic fingerprints.

Forty-two yeast strains from 27 species belonging to seven genera, selected for their ability to grow in 10% NaCl, have been analysed for their resistance to salt concentrations up to 5 M, by calculating the Minimum Inhibitory Concentrations (MIC). Using eight different NaCl concentrations from 0 to 5M, results show that halotolerance (MIC) ranges from 1.7 to 3.8 M NaCl, with an avera ge around 2.5 M and confirm that the most halotolerant strains belong to the speciesDebaryomyces hansenii. Since a real halophily could not be found in these isolates, and is generally questioned to be present among the yeast, the effects of NaCl has been measured as salt enhancement effect on growth (MSE), which is defined as the rate between the growth at a given NaCl concentration and theowth in the medium without addition of salt. The implications of these findings in food microbial ecology and technology are discussed.

Different phenotypical or molecular techniques can be used to describe and classify microorganisms for taxonomic, phylogenetic or genetic purposes. In yeast taxonomy the official hierarchic classification, based on morphological and physiological characters, is used together with more convenient molecular techniques such as the DNA sequencing. The question on whether these procedures produce coherent classifications is critical both to interpret taxonomic data consistently and to outline species correctly. In this paper, a set of type strains from the major genera of the budding hemiascomycetes yeast is examined with a series of physiological and molecular techniques, widely employed in taxonomy, in order to compare the among-strains correlations obtained with different methods. Results showed that the level of correlation among different techniques is relatively low, showing that different classifications and species organization could be obtained with diverse approaches. This is particularly interesting, considering that the official description of the yeast species is based on characters different from those becoming increasingly popular in the routine identification.

Aims: Two different strain characterization techniques, random amplified polymorphic DNA (RAPD) and killer toxin sensitivity (KTS), were compared to assess their typing performance using a set of 30 certified Saccharomyces cerevisiae strains. Methods and Results: A sequential random resampling procedure was employed to subdivide the 32 descriptors in eight sets, in order to compare the differential performances of the two techniques with diverse number of characters. Results showed that RAPD performs better than killer, although the complete differentiation of the strains under study could be obtained only by combining profiles from the two techniques Conclusions: The combination of different typing techniques was useful when discriminating similar organisms. In such cases, the introduction of a second typing technique can be more advantageous than increasing the number of characters obtained with a single method. Significance and Impact of the Study: The distribution of among-strains pairwise distances and the relative performance of the two techniques has implications for the study of biodiversity, taxonomy and microbial ecology.

It has come to the authors' attention that errors were made in determining the rDNA sequences that served as the basis of Fig. 4 in the above mentioned article, Ganter et al. 2004. The rDNA D1/D2 region was amplified with primers NL1 and NL4 and sequenced in a single direction using NL1. The quality of each nucleotide signal was assessed using the PHRED software and only signals with over 99% support were accepted. This procedure led us to trim parts of the external regions of the sequences, but could not detect incorrect insertions or deletions appearing as elongations or shortenings of repetitive strings (e.g., a GGGG or a GG in place of a correct GGG). All 36 strains have been re-sequenced under the following conditions. Figure 1 The D1/D2 domain of the LSU rDNA repeat was amplified with NL1 and NL4 primers, then sequencing was carried out for each strand with the same primers. For each strain, the forward NL1 sequence and the reverse-complement NL4 sequence …