Precision mass measurements of magnesium isotopes and implications on the validity of the Isobaric Mass Multiplet Equation

If the mass excess of neutron-deficient nuclei and their neutron-rich mirror partners are both known, it can be shown that deviations of the Isobaric Mass Multiplet Equation (IMME) in the form of a cubic term can be probed. Such a cubic term was probed by using the atomic mass of neutron-rich magnesium isotopes measured using the TITAN Penning trap and the recently measured proton-separation energies of $^{29}$Cl and $^{30}$Ar. The atomic mass of $^{27}$Mg was found to be within 1.6$\sigma$ of the value stated in the Atomic Mass Evaluation. The atomic masses of $^{28,29}$Mg were measured to be both within 1$\sigma$, while being 8 and 34 times more precise, respectively. Using the $^{29}$Mg mass excess and previous measurements of $^{29}$Cl we uncovered a cubic coefficient of $d$ = 28(7) keV, which is the largest known cubic coefficient of the IMME. This departure, however, could also be caused by experimental data with unknown systematic errors. Hence there is a need to confirm the mass excess of $^{28}$S and the one-neutron separation energy of $^{29}$Cl, which have both come from a single measurement. Finally, our results were compared to ab initio calculations from the valence-space in-medium similarity renormalization group, resulting in a good agreement.Comment: 7 pages, 3 figure

Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats

OBJECTIVE: Progesterone (P4) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed for the alleviation of a variety of gynecological issues, but very few studies have characterized natural compounds in terms of their ability to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid that functions as a non-steroidal selective progesterone receptor modulator (SPRM) in vitro. This study investigated the molecular and physiological effects of kaempferol in the ovariectomized rat uteri.METHODS: Since genistein is a phytoestrogen that was previously demonstrated to increase uterine weight and proliferation, the ability of kaempferol to block genistein action in the uterus was investigated. Analyses of proliferation, steroid receptor expression, and induction of well-established PR-regulated targets Areg and Hand2 were completed using histological analysis and qPCR gene induction experiments. In addition, kaempferol in silico binding analysis was completed for PR. The activation of estrogen and androgen receptor signalling was determined in vitro.RESULTS: Molecular docking analysis confirmed that kaempferol adopts poses that are consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced expression of PR regulated transcriptional targets in the ovariectomized rat uteri, including Hand2 and Areg. Consistent with progesterone-l ke activity, kaempferol attenuated genistein-induced uterine luminal epithelial proliferation without increasing uterine weight. Kaempferol signalled without down regulating PR expression in vitro and in vivo and without activating estrogen and androgen receptors.CONCLUSION: Taken together, these data suggest that kaempferol is a unique natural PR modulator that activates PR signaling in vitro and in vivo without triggering PR degradation.</p

Epithelial Ovarian Cancer Experimental Models

Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge

Spontaneous Transformation of Murine Oviductal Epithelial Cells: A Model System to Investigate the Onset of Fallopian-Derived Tumors

High-grade serous carcinoma (HGSC) is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs) are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, a spontaneous HGSC model has not been described. Apart from a subpopulation of genetically predisposed women, most women develop ovarian cancer spontaneously, which is associated with aging and lifetime ovulations. A murine oviductal cell line (MOELOW) was developed and continuously passaged in culture to mimic cellular aging (MOEHIGH). The MOEHIGH cellular model exhibited a loss of acetylated tubulin consistent with an outgrowth of secretory epithelial cells in culture. MOEHIGH cells proliferated significantly faster than MOELOW, and the MOEHIGH cells produced more 2D foci and 3D soft agar colonies as compared to MOELOW. MOEHIGH were xenografted into athymic female nude mice both in the subcutaneous and the intraperiteonal compartments. Only the subcutaneous grafts formed tumors that were negative for cytokeratin, but positive for oviductal markers such as oviductal glycoprotein 1 and Pax8. These tumors were considered to be poorly differentiated carcinoma. The differential molecular profiles between MOEHIGH and MOELOW were determined using RNA-Seq and confirmed by protein expression to uncover pathways important in transformation, like the p53 pathway, the FOXM1 pathway, WNT signaling, and splicing. MOEHIGH had enhanced protein expression of c-myc, Cyclin E, p53 and FOXM1 with reduced expression of p21. MOEHIGH were also less sensitive to cisplatin and DMBA, which induce lesions typically repaired by base-excision repair. A model of spontaneous tumorogenesis was generated starting with normal oviductal cells. Their transition to cancer involved alterations in pathways associated with high-grade serous cancer in humans

The Effect of Work Rate on Oxygen Uptake Kinetics During Exhaustive Severe Intensity Cycling Exercise

The effect of work rate on oxygen uptake kinetics during exhaustive severe intensity cycling exercise Jennifer L. Sylvester, Samantha D. Burdette, Steven W. Cross, Nosa O. Idemudia, John, H. Curtis, Jakob L. Vingren, David W. Hill. Applied Physiology Laboratory, University of North Texas, Denton, TX During exhaustive severe intensity exercise, the oxygen uptake (VO2) increases exponentially, with a time constant of ~30 s. After ~1 to 2 min, a slow component emerges and drives the VO2 to its maximum. There are clear differences in the VO2 response profile across exercise intensity domains. These disparities might not be attributable to metabolic demand but, rather, to characteristics of the various intensity domains, such as the consequences of lactic acid production. PURPOSE: To investigate the role of exercise intensity on the VO2 response profile at intensities wholly within the severe domain. METHODS: Four women (mean ± SD: age 22 ± 2 years, height 167 ± 7 cm, mass 66 ± 5 kg) and eight men (age 23 ± 2 yr, height 179 ± 9 cm, mass 78 ± 10 kg) performed exhaustive constant-power cycle ergometer tests at two different severe intensity work rates (263 ± 78 W and 214 ± 64 W). Smoothed breath-by-breath VO2 data were fitted to a two-component (primary response and slow component) model using iterative regression. RESULTS: Times to exhaustion were 217 ± 27 s and 590 ± 82 s, respectively. The VO2max values were the same at the two different work rates (2973 ± 691 ml·min-1 and 3011 ± 728 ml·min-1). The amplitude of the primary response was greater (p \u3c 0.05) at the higher work rate (2095 ± 716 ml·min-1) than at the lower work rate (1857 ± 618 ml·min-1) and the amplitude of the slow component was smaller (367 ± 177 ml·min-1 vs 645 ± 347 ml·min-1). In addition, the time delay before the emergence of the slow component was shorter at the higher work rate (92 ± 22 s vs 116 ± 42 s). CONCLUSION: The results show that exercise intensity per se affects the VO2 response profile within the severe intensity domain and suggest that metabolic demand drives the primary response of VO2 kinetics within this domain. Category to be judged: Master\u27