No abstract

In early vertebrate development, apicobasally polarised blastomeres divide to produce inner non-polarised cells and outer polarised cells that follow different fates. How the polarity of these early blastomeres is established is not known. We have examined the role of Crumbs3, Lgl2 and the apical aPKC in the polarisation of frog blastomeres. Lgl2 localises to the basolateral membrane of blastomeres, while Crumbs3 localises to the apical and basolateral membranes. Overexpression aPKC and Crumbs3 expands the apical domain at the expense of the basolateral and repositions tight junctions in the new apical-basolateral interface. Loss of aPKC function causes loss of apical markers and redirects basolateral markers ectopically to the apical membrane. Cell polarity and tight junctions, but not cell adhesion,are lost and outer polarised cells become inner-like apolar cells. Overexpression of Xenopus Lgl2 phenocopies the aPKCknockout, suggesting that Lgl2 and aPKC act antagonistically. This was confirmed by showing that aPKC and Lgl2 can inhibit the localisation of each other and that Lgl2 rescues the apicalisation caused by aPKC. We conclude that an instrumental antagonistic interaction between aPKC and Lgl2 defines apicobasal polarity in early vertebrate development.

Endometriosis currently affects ∼5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed.

PurposeA study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.Methods and materialsTen institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.ResultsFor all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.ConclusionsThe investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.

The use of FFF beams for stereotactic radiation therapy of nonsmall cell lung cancer patients yielded dose distributions qualitatively comparable to flattened beams and significantly reduced treatment delivery time. Utilizing the X6FFF beam improved conformity of dose distribution. On the other hand, X10FFF beam offered a slight improvement in treatment efficiency, and lower skin and peripheral dose. All effects were relatively small.