The Sexual Experiences Survey (SES), the most widely used measure of unwanted sexual experiences, was recently updated (Koss et al., 2007). The purpose of this study was to provide psychometric data on the updated Sexual Experiences Survey-Short Form Perpetration (SES-SFP) and the Sexual Experiences Survey-Short Form Victimization (SES-SFV). Men (n = 136) and women (n = 433) were randomly assigned to in-person or Internet formats of administration for 3 measurement points. Women completed victimization surveys and trauma measures. Men completed perpetration surveys and attitude/ personality measures. Results supported the validity and reliability of both the SES-SFV with women and the SES-SFP with men. Further research is needed regarding the use of the SES-SFV with men and the SES-SFP with women.

Human microbiomes are predicted to assemble in a reproducible and ordered manner yet there is limited knowledge on the development of the complex bacterial communities that constitute the oral microbiome. The oral microbiome plays major roles in many oral diseases including early childhood caries (ECC), which afflicts up to 70% of children in some countries. Saliva contains oral bacteria that are indicative of the whole oral microbiome and may have the ability to reflect the dysbiosis in supragingival plaque communities that initiates the clinical manifestations of ECC. The aim of this study was to determine the assembly of the oral microbiome during the first four years of life and compare it with the clinical development of ECC. The oral microbiomes of 134 children enrolled in a birth cohort study were determined at six ages between two months and four years-of-age and their mother’s oral microbiome was determined at a single time point. We identified and quantified 356 operational taxonomic units (OTUs) of bacteria in saliva by sequencing the V4 region of the bacterial 16S RNA genes. Bacterial alpha diversity increased from a mean of 31 OTUs in the saliva of infants at 1.9 months-of-age to 84 OTUs at 39 months-of-age. The oral microbiome showed a distinct shift in composition as the children matured. The microbiome data were compared with the clinical development of ECC in the cohort at 39, 48, and 60 months-of-age as determined by ICDAS-II assessment. Streptococcus mutans was the most discriminatory oral bacterial species between health and current disease, with an increased abundance in disease. Overall our study demonstrates an ordered temporal development of the oral microbiome, describes a limited core oral microbiome and indicates that saliva testing of infants may help predict ECC risk.

Promoter hypermethylation of the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to compare three distinct yet related indices for measuring AGT to determine if these assays could be used interchangeably when AGT status is to be used to guide chemotherapeutic decisions. Real-time methylation-specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal B-actin control, was used to quantitate AGT hypermethylation in 32 glioma samples. Data were compared with AGT enzyme activity as well as immunohistochemical detection of AGT protein from the same samples. Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples evaluable by MSP. Low-level AGT, defined as <20% nuclear AGT staining by immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%) had low levels of AGT activity. Correlation of immunohistochemistry to AGT activity was statistically significant (P = 0.014) as was the correlation of immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity (P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP data based on prognostic groups, where good prognosis was represented by an immunohistochemistry of <20% and an MSP ratio >12, showed no significant relationship (P = 0.214), suggesting that one assay cannot be used interchangeably for another. The observed discordance between respective measures of AGT based on prognosis supports further standardization of AGT assays designed to guide therapeutic practice. The data also suggest that consideration be given to the large population of AGT-expressing cells within samples when therapeutic strategies based on tumor methylation are used. [Mol Cancer Ther 2006;5(10):2531 -9]

Temozolomide is a DNA-methylating agent used in the treatment of malignant gliomas. In this study, we have examined if inhibition of poly(ADP-ribose) polymerase (PARP) could increase the cytotoxicity of temozolomide, particularly in cells deficient in DNA mismatch repair. Athymic mice, transplanted with mismatch repairproficient or deficient [D-245 MG (PR)] xenografts, were treated with a combination of temozolomide and the PARP inhibitor, INO-1001. For the tumors deficient in mismatch repair, the most effective dose of INO-1001 was found to be 150 mg/kg, given i.p. thrice at 4-hour intervals with the first injection in combination with 262.5 mg/kg temozolomide (0.75 LD 10 ). This dose of temozolomide by itself induced no partial regressions and a 4-day growth delay. In two separate experiments, the combination therapy increased the growth delay by 21.6 and 9.7 days with partial regressions observed in four of eight and three of nine mice, respectively. The addition of INO-1001 had a more modest, yet statistically significant, increase in tumor growth delay in the mismatch repair -proficient xenografts. In these experiments, mice were treated with a lower amount of temozolomide (88 mg/kg), which resulted in growth delays of 43.1 and 39.2 days. When the temozolomide treatment was in combination with 200 mg/kg INO-1001, there was an increase in growth delay to 48.9 and 45.7 days, respectively. These results suggest that inhibition of PARP may increase the efficacy of temozolomide in the treatment of malignant gliomas, particularly in tumors deficient in DNA mismatch repair. [Mol Cancer Ther 2005;4(9):1364-8]

Purpose: A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temozolomide regardless of AGT activity. The purpose of this study was to determine the role of MMR deficiency in mediating resistance in samples from patients with both newly diagnosed malignant gliomas and those who have failed temozolomide therapy. Experimental Design: The roles of AGT and MMR deficiency in mediating resistance in glioblastoma multiforme were assessed by immunohistochemistry and microsatellite instability (MSI), respectively. The mutation status of the MSH6 gene, a proposed correlate of temozolomide resistance, was determined by direct sequencing and compared with data from immunofluorescent detection of MSH6 protein and reverse transcription-PCR amplification of MSH6 RNA. Results: Seventy percent of newly diagnosed and 78 % of failed-therapy glioblastoma multiforme samples expressed nuclear AGT protein in z20% of cells analyzed, suggesting alternate means of resistance in 20% to 30% of cases. Single loci MSI was observed in 3% of patient samples; no sample showed the presence of high MSI. MSI was not shown to correlate with MSH6 mutation or loss of MSH6 protein expression. Conclusions: Although high AGT levels may mediate resistance in a portion of these samples, MMR deficiency does not seem to be responsible for mediating temozolomide resistance in adult malignant glioma. Accordingly, the presence of a fraction of samples exhibiting both lowAGT expression and MMR proficiency suggests that additional mechanisms of temozolomide resistance are operational in the clinic.

The rRNA genes in most eucaryotic organisms are present in a tandem array. There is substantial evidence that transcription of one of these genes may not be independent of transcription of others. In particular, in the yeast Saccharomyces cerevisiae, the enhancer of rRNA transcription that lies 2.2 kilobases 5' of the transcription initiation site is at least partly within the upstream transcription unit. The transcription by RNA polymerase II of a wide variety of genes is profoundly influenced by cis-acting short-nucleotide sequences called enhancer elements that can lie upstream or downstream of the transcription unit, at a distance of up to several kilobases. In many cases, the enhancer elements bind protein factors that are necessary for enhancer function. Although a number of models have been proposed (reviewed in reference 30), a clear understanding of enhancer function is not at hand.Two features distinguish rRNA genes from other genes in the eucaryotic cell. They are transcribed by a specific enzyme, RNA polymerase I, and they are arranged in a tandem array. This unique genetic structure has led to speculation that transcription of an individual gene is not independent of transcription of the neighboring genes; e.g., termination at one transcription unit may lead directly to initiation at the neighboring downstream promoter (7,12,15, 26).We have identified a sequence element, specific for RNA polymerase I, that has many of the characteristics of an RNA polymerase II enhancer (9, 10). In this paper, we explore aspects of the function of RNA polymerase I and its enhancer to ask about the parallels between polymerase I and polymerase II enhancers and about the importance of the tandemness of rRNA genes to polymerase I activity.Transcription by RNA polymerase I has been reviewed recently (38). The spacers between individual rRNA transcription units vary in length from 2 kilobase pairs (kb) (yeasts) to >30 kb (mammals). Within them are found a variety of sequence elements that influence the level of transcription. In Xenopus laevis, for example, these include several copies of a sequence closely related to the promoter, dubbed spacer promoters (6,7,22,23,29,33), each followed by about 10 copies of a 60-to 81-base-pair (bp) repeat, that behave in some respects like enhancer elements (22,23,29). The spacer promoters are curious because although they can give rise to transcripts and can stimulate transcription from an adjacent real promoter (6,7,29), the transcription from the spacer promoter seems not to be involved in this stimulation (7,25). Repetitive elements, some related to the promoter, have also been found in the nontranscribed spacer * Corresponding author. t Present address:

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