BackgroundPrevious elegant studies performed in the fission yeast Schizosaccharomyces pombe have identified a requirement for heterochromatin protein 1 (HP1) for spindle pole formation and appropriate cell division. In mammalian cells, HP1γ has been implicated in both somatic and germ cell proliferation. High levels of HP1γ protein associate with enhanced cell proliferation and oncogenesis, while its genetic inactivation results in meiotic and mitotic failure. However, the regulation of HP1γ by kinases, critical for supporting mitotic progression, remains to be fully characterized.ResultsWe report for the first time that during mitotic cell division, HP1γ colocalizes and is phosphorylated at serine 83 (Ser83) in G2/M phase by Aurora A. Since Aurora A regulates both cell proliferation and mitotic aberrations, we evaluated the role of HP1γ in the regulation of these phenomena using siRNA-mediated knockdown, as well as phosphomimetic and nonphosphorylatable site-directed mutants. We found that genetic downregulation of HP1γ, which decreases the levels of phosphorylation of HP1γ at Ser83 (P-Ser83-HP1γ), results in mitotic aberrations that can be rescued by reintroducing wild type HP1γ, but not the nonphosphorylatable S83A-HP1γ mutant. In addition, proliferation assays showed that the phosphomimetic S83D-HP1γ increases 5-ethynyl-2´-deoxyuridine (EdU) incorporation, whereas the nonphosphorylatable S83A-HP1γ mutant abrogates this effect. Genome-wide expression profiling revealed that the effects of these mutants on mitotic functions are congruently reflected in G2/M gene expression networks in a manner that mimics the on and off states for P-Ser83-HP1γ.ConclusionsThis is the first description of a mitotic Aurora A-HP1γ pathway, whose integrity is necessary for the execution of proper somatic cell division, providing insight into specific types of posttranslational modifications that associate to distinct functional outcomes of this important chromatin protein.

Objective To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Design Case-control study (Mayo Clinic Ovarian Cancer Study). Setting Ongoing academic study of ovarian cancer. Patient(s) A total of 1900 women (1028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. Intervention(s) None Main outcome measure(s) Effect of infertility history, use of fertility drugs and oral contraception and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Result(s) Among women who had a history of infertility, use of fertility drugs was reported by 24% (44/182) of controls and 17% (38/226) of cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared to infertile women who did not use fertility drugs, adjusted odds ratio was 0.64 (95% CI 0.37, 1.11). Findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. Conclusion(s) We did not find any significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation.

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Mineral oil overlay microdrop is commonly used during in vitro fertilization (IVF) procedures. Though mineral oil appears homogeneous, it is an undefined product that can vary in quality. Here, we describe the history, chemistry, processing, and optimal use of mineral oil for IVF and embryo culture.