Using the murine embryonal stem cell system, we have identified a novel gene encoding a highly divergent member of the ␤-chemokine family of proinflammatory mediators and have called this protein ESkine. Much of the coding sequence for ESkine overlaps with the 3-end of a novel interleukin 11 receptor ␣-like sequence on murine chromosome 4. ESkine is produced as two splice variants. One of these variants encodes a classical chemokine with an associated signal peptide, while the other variant (PESKY) possesses the main body of the chemokine but has replaced the signal peptide with an alternative stretch of amino acids that allows for nuclear targeting of this isoform. This differential splicing arises as a result of alternative 5 exon usage. These differentially spliced forms are expressed at discrete tissue loci. Thus, while ESkine is highly expressed in the placenta, PESKY is mainly expressed in the Testes and brain and weakly in the developing embryo. Studies on the proinflammatory properties of ESkine reveal it to be active in inducing polarization of CD4 ؉ T cells but to be inactive on other hemopoietic cellular populations.

Human papillomaviruses (HPV) are causative agents in a variety of human diseases; for example over 99% of cervical carcinomas contain HPV DNA sequences. Often in cervical carcinoma the HPV genome is integrated into the host genome resulting in unregulated expression of the viral transforming proteins E6 and E7. Therefore viral integration is a step toward HPV-induced carcinogenesis. Integration of the HPV genome could occur following double-strand DNA breaks that could arise during viral DNA replication. We investigated the fidelity of HPV 16 E1-and E2-mediated DNA replication of non-damaged and UVC-damaged templates in a variety of cell lines with different genetic backgrounds; C33a (derived from an HPV-negative cervical carcinoma), XP30RO (deficient in the by-pass polymerase (pol )), XP30 (expressing a restored wild-type pol ), XP12RO (nucleotide excision repair defective), and MRC5 (derived from a 14-week-old human fetus). The results demonstrate that the fidelity of E1-and E2-mediated DNA replication is reflective of the genetic background in which the assays are carried out. Human papilloma viruses (HPVs) 1 are small doublestranded DNA tumor viruses that are causative agents in a variety of human diseases. Over 99% of cervical carcinomas contain HPV sequences; these are of the high-risk type with HPV16 being the most common. The low risk HPVs are causative agents of genital warts, and HPV6/11 are the most commonly found in this disease (1). HPVs are maintained as episomal circular DNA molecules in infected cells and are replicated by the viral proteins E1 and E2 (2, 3). The E2 protein forms homodimers and recognizes and binds to 12bp palindromic DNA sequences in the transcriptional control region of HPV (4). E2 can then regulate transcription from the adjacent promoter that controls the expression of the HPV oncogenes E6 and E7; E2 can either activate or repress transcription depending upon E2 protein levels and the cell type (5, 6). As well as regulating transcription E2 is also essential for replication of the viral genome; there are three E2 DNA binding sequences surrounding the viral origin (ori) of replication and a physical interaction between E2 and E1 results in recruitment of E1 to the ori sequence (7,8,9). Following recruitment by E2 the E1 protein interacts with the ori DNA sequence and then forms a hexameric complex required for replication of the viral genome by virtue of its helicase activity (10). E1 is known to interact with subunits of DNA polymerase-␣ and with components of the Swi/Snf complex in order to activate DNA replication (11,12).In many HPV-induced cervical cancers the HPV genome is found integrated into the host genome. This integration usually deletes the coding sequence for the E2 protein and results in elevated expression of the viral oncoproteins E6 and E7 (13). It is proposed that increased E6 and E7 levels are involved in progression toward carcinoma. Therefore the loss of episomal status of the HPV genome is an important step on the way to carcinogenesis. The integration i...

Bracken fern is the environmental co-carcinogen of BPV-4 in the induction of neoplasias of the upper alimentary canal of cattle. The¯avonoid quercetin is one of the most potent and best characterised mutagens present in the fern. We have shown that transfection with BPV-4 DNA and exposure to a single dose of quercetin leads to tumorigenic transformation of primary bovine cells. We now show that quercetin induces cell cycle arrest and up-regulates transcription from the BPV-4 long control region (LCR). This up-regulation is mediated by a 21 nucleotide-long cis-element in the LCR, designated QRE-1, which is located immediately downstream of the TATA box. Cellular proteins bind to QRE-1 and removal or substitution of QRE-1 lead to the abrogation of the response to quercetin. As expression of the viral oncogenes is controlled by the LCR, perturbation in this control and increased oncoprotein expression are likely to contribute to fully malignant cell transformation by overcoming the cell cycle arrest induced by quercetin, thus forcing damaged cells to proliferate.

Background:The aim of this study was to compare thick versus thin connective tissue grafts (CTG) for the treatment of gingival recession, over a 3-month period.Methods: Forty-two CTG procedures were performed on single tooth Miller Class I or II recession defects at either premolar or anterior sites in 30 individuals. Procedures were randomized (1:1 ratio) to CTG thickness of 1 or 2 mm (parallel group design). Primary outcomes were the change in the width of the zone of keratinized tissue and the amount of root coverage achieved 3 months postoperatively at the recipient site. Secondary outcomes included change in the thickness of keratinized tissue at 3 months and patient-reported outcomes, such as pain, bleeding, and swelling at both the recipient and donor sites at 1 week, 2 weeks, 1 month, and 3 months.Results: No significant differences were found between the two groups for any of the primary or secondary outcomes. Mean root coverage achieved was 2.1 ± 0.2 mm in the 1-mm thick group and 2.5 ± 0.2 mm in the 2-mm thick group (P = 0.33).Keratinized tissue width was increased by 2.2 ± 0.2 mm in the 1-mm thick group and by 2.7 ± 0.3 mm in the 2-mm thick group (P = 0.18). Keratinized tissue thickness was increased by 1.0 ± 0.1 mm and by 1.2 ± 0.1 mm in the 1-and 2-mm thick groups, respectively (P = 0.09).Conclusion: Within the current study limitations, our results suggest that similar root coverage and increase in the width and thickness of keratinized tissue can be achieved at 3 months whether a 1-or 2-mm thick CTG is used. K E Y W O R D Sgingival recession, patient reported outcomes, randomized clinical trial, tissue grafts 966