Role of transforming growth factor beta in ovarian surface epithelium biology and ovarian cancer

Ovarian cancers arise out of the ovarian surface epithelium (OSE), which is the single layer of epithelial cells covering the ovary. These cells go through repeated cycles of proliferation with the growth and rupture of ovarian follicles. One growth factor involved in the regulation of OSE is transforming growth factor beta (TGFbeta). The different isoforms of TGFbeta (TGFbeta1, TGFbeta2 and TGFbeta3) and its receptor are all present in both OSE and the underlying ovarian surface stroma. The levels of the TGFbeta isoforms and receptors are regulated independently of each other in these different ovarian tissues. Observations suggest the existence of multiple autocrine/paracrine TGFbeta signalling loops. TGFbeta acts to inhibit proliferation of normal OSE and early stage ovarian carcinomas. Conversely, in later stage ovarian cancer the inhibitory actions of TGFbeta on epithelial proliferation have been overcome, while TGFbeta is able to promote malignant neoplastic behaviours. The regulation of TGFbeta signalling by ovarian steroid hormones may be one mechanism by which the OSE responds to cyclic changes in the underlying follicles

Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology Unified Evolution Theory

The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology

Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development

The growth and development of follicles within the ovary are highly dependent on autocrine and paracrine signaling involving growth factors from granulosa cells, theca cells, stromal interstitial cells, and the oocytes. The growth factor bone morphogenetic protein-4 (BMP-4) and its receptor (BMPR-IB) have been detected in ovaries, and a mutation in BMPR-IB has been associated with abnormal ovulation rate. The objective of the current study was to examine the role that BMP-4 plays in the early stages of primordial follicle development. Ovaries from 4-day-old rats were placed into a whole-ovary organ culture system for 2 wk to investigate the effect that treatment with exogenous BMP-4 has on early follicle development. BMP-4-treated ovaries had a significantly higher proportion of developing primary follicles and fewer arrested primordial follicles than did untreated controls. This indicates that BMP-4 promotes primordial follicle development and the primordial-to-primary follicle transition. Ovaries were also treated with neutralizing antibody against BMP-4 to determine effects of removing endogenously produced BMP-4. Interestingly, ovaries treated with BMP-4 antibody were markedly smaller than controls. This was associated with a progressive loss of oocytes and primordial follicles, a progressive increase in cellular apoptosis, and an accompanying loss of normal ovarian tissue morphology over time. Immunocytochemistry localized BMP-4 protein to isolated stromal cell populations, selected stromal cells (i.e., pretheca cells) associated with developing primordial follicles, and the basement membrane of follicles. Ovaries were treated with BMP-4 and RNA collected after organ culture to determine whether BMP-4 signaling affects expression of other growth factors. Kit ligand and basic fibroblast growth factor expression was unchanged, but TGFalpha expression was decreased in whole ovaries. Taken together, these data suggest that BMP-4 plays an important role in promoting the survival and development of primordial follicles in the neonatal ovary

Epigenetic Transgenerational Inheritance of Obesity Susceptibility

The prevalence of obesity and associated diseases has reached pandemic levels. Obesity is often associated with overnutrition and a sedentary lifestyle, but clearly other factors also increase the susceptibility of metabolic disease states. Ancestral and direct exposures to environmental toxicants and altered nutrition have been shown to increase susceptibility for obesity and metabolic dysregulation. Environmental insults can reprogram the epigenome of the germline (sperm and eggs), which transmits the susceptibility for disease to future generations through epigenetic transgenerational inheritance. In this review, we discuss current evidence and molecular mechanisms for epigenetic transgenerational inheritance of obesity susceptibility. Understanding ancestral environmental insults and epigenetic transgenerational impacts on future generations will be critical to fully understand the etiology of obesity and to develop preventative therapy options.The prevalence of obesity has increased dramatically over the past 30 years, and cannot be explained by genetics, diet, and exercise alone.A variety of early life and in utero exposures to environmental insults can change metabolic outcomes through developmental epigenetic reprogramming.Epigenetic transgenerational inheritance of obesity has been observed following ancestral exposure to a high-fat diet, malnutrition, and several environmental toxicants.Unique obesity-specific sperm epimutation signatures have been identified in the transgenerational F3 generation of animals ancestrally exposed to environmental toxicants.Numerous genes modified by DNA methylation in a variety of phenotypes and ancestral exposures have been found to be potential novel modulators of adipocyte (fat cell) metabolism and function

Direct UV observations of the circumstellar envelope of alpha Orionis

Observations were made in the IUE LWP camera, low dispersion mode, with alpha Ori being offset various distances from the center of the Long Wavelength Large Aperture along its major axis. Signal was acquired at all offset positions and is comprised of unequal components of background/dark counts, telescope-scattered light, and scattered light emanating from the extended circumstellar shell. The star is known from optical and infrared observations to possess an extended, arc-minute sized, shell of cool material. Attempts to observe this shell with the IUE are described, although the deconvolution of the stellar signal from the telescope scattered light requires further calibration effort

Transferrin gene expression and synthesis by cultured choroid plexus epithelial cells Regulation by serotonin and cyclic adenosine 3',5'-monophosphate

Primary cultures of rat choroid plexus epithelial cells were established and used to investigate the role of the choroid plexus in the synthesis and secretion of transferrin. Transferrin gene expression was determined by a Northern blot analysis with a transferrin cRNA probe. A single transferrin mRNA species was detected and found to be the same size as the transcripts in the liver and Sertoli cells. Immunoprecipitation of radiolabeled secreted proteins with an antiserum transferrin antibody demonstrated that cultured choroid plexus epithelial cells synthesize and secrete a 70-kDa species of transferrin. Levels of transferrin secretion by rat choroid plexus epithelial cells in culture were measured by radioimmunoassay. Treatment of the choroid plexus epithelial cells in culture with cell-permeable cAMP analogs or serotonin led to time- and concentration-dependent changes in the levels of transferrin in the medium. Dibutyryl-cAMP and 8-bromo-cAMP decreased the levels of transferrin synthesized and secreted by choroid plexus epithelial cells with an EC50 value of 30 nM. Serotonin, however, increased the levels of transferrin with an EC50 value of 100 nM. A concomitant change in transferrin mRNA concentrations was observed in response to serotonin. These data suggest that the synthesis of transferrin by the choroid plexus is reciprocally regulated by the neurotransmitter serotonin and by regulatory agents coupled to adenylate cyclase. Regulatory agents such as serotonin may have a critical role in modulating the proteins synthesized by the choroid plexus, thereby influencing the composition of the cerebrospinal fluid

Localization dynamics of fluids in random confinement

The dynamics of two-dimensional fluids confined within a random matrix of obstacles is investigated using both colloidal model experiments and molecular dynamics simulations. By varying fluid and matrix area fractions in the experiment, we find delocalized tracer particle dynamics at small matrix area fractions and localized motion of the tracers at high matrix area fractions. In the delocalized region, the dynamics is subdiffusive at intermediate times, and diffusive at long times, while in the localized regime, trapping in finite pockets of the matrix is observed. These observations are found to agree with the simulation of an ideal gas confined in a weakly correlated matrix. Our results show that Lorentz gas systems with soft interactions are exhibiting a smoothening of the critical dynamics and consequently a rounded delocalization-to-localization transition.Comment: 5 pages, 3 figure

Whose Ideas? Whose Words? Authorship of Ronald Reagan's Radio Addresses

Statistic