Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets

Lipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive channel MscL, the high-pressure threshold channel. We restrict lipid-chain access to the nano-pockets by mutagenesis and sulfhydryl modification, and monitor channel conformation by PELDOR/DEER spectroscopy. For a single site located at the entrance of the nano-pockets and distal to the channel pore we generate an allosteric response in the absence of tension. Single-channel recordings reveal a significant decrease in the pressure activation threshold of the modified channel and a sub-conducting state in the absence of applied tension. Threshold is restored to wild-type levels upon reduction of the sulfhydryl modification. The modification associated with the conformational change restricts lipid access to the nano-pocket, interrupting the contact between the membrane and the channel that mediates mechanosensitivity

Robust inspection for invasive species with a limited budget

Invasive species can inflict significant costs on agriculture. Approaches to prevent introduction and/or to contain introduced species can also be very costly. Approaches to managing invasive-species problems include pre-emptive actions against potential invaders in foreign locales, border activities such as inspections to prevent introductions across international boundaries, domestic monitoring and control to prevent establishment if introductions occur, management of domestically established introductions through use of various forms of interference (e.g., vector control, enemies, pathogens, symbionts, endophytes, hosts, and/or physical factors perhaps as part of areawide management programs), and combinations of these approaches. This paper focuses on providing applicable quantitative decision support to the process of establishing efficient protocols for border protection under the severe uncertainty and resource constraints that characterize the inspection process. In this paper, a hybrid infogap model is used in conjunction with stochastic dominance to develop a cost-effective protocol for invasive-species detection efforts. The model is illustrated by a detection problem faced at international ports. Problem characteristics advantageous to robust preparedness protocols are investigate

Hoes to Herbicides: Economics of Evolving Weed Management in the United States

Weed control is the most labor-demanding aspect of row-crop agriculture in the absence of herbicides. The past century has seen weed management in the United States evolve from horse-drawn cultivators to broad-spectrum herbicides on herbicide-tolerant crops. Three waves of technological change have driven the evolution. Current weed control technologies are Mechanical (for organic products), Chemical (when herbicide resistant weeds require multiple herbicides for effective weed control), and Genetic + Chemical (herbicide-tolerant crop). Cost analysis for a representative Midwestern farm shows that these three systems have decreasing requirements in both capital and labor