55 research outputs found

    Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression

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    The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage ∼7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well

    In-home evaluation of efficacy and titration of a mandibular advancement device for obstructive sleep apnea

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    There is increasing evidence that mandibular advancement devices (MADs) can be an effective treatment for some patients with obstructive sleep apnea, a highly prevalent chronic disease. In this study, the objectives were to objectively assess the effectiveness of MAD therapy using a limited channel recorder, and to develop a model for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Thirty patients were prospectively recruited and studied at two independent dentist offices and the participants’ homes. Subjects wore the ARES Unicorder for two nights before insertion of the MAD, and again when the dentist determined that the patient had reached the titration endpoint. Self-reported measures of depression, sleepiness, and quality of life were obtained pre- and posttreatment. The reviewer was blinded to the study status while the physiological signals were being visually inspected. Significant reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut-off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or had a posttreatment AHI ≤ 10. Significant differences in body mass index, weight, and neck circumference in patients with posttreatment AHIs above and below a clinical cut-off of five were identified. The linear regression used to predict the posttreatment AHI using pretreatment data resulted in an R2 of 0.68. The model correctly predicted two patients who were unable to obtain a posttreatment AHI of 10 or less. This study was designed to demonstrate two models of collaboration between a dental sleep medicine specialist and a sleep medicine physician in the monitoring of a patient treated with a MAD. The outcome data suggest that the limited channel recording system can be used as an alternative to laboratory polysomnography to reduce the cost of MAD treatment, and to improve the quality and consistency of posttreatment patient care
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