Mesenchymal stem cells (MSCs), precursor cells resident in the bone marrow, have the capacity to differentiate into bone, cartilage, fat, and connective tissue. We have recently reported that MSCs from "healthy" donors differ from cells obtained from osteoporotic postmenopausal women in their proliferation rate, mitogenic response to osteogenic growth factors, and potential to mineralize. The purpose of this study was to examine the factors that explain the differential capacity of MSCs derived from "healthy" control and osteoporotic postmenopausal women to support mineralization. In addition, we examined the factors that regulate the differentiation of osteoporotic cells into adipocytes. For this purpose, we isolated MSCs from bone marrow of donors and analyzed the synthesis and deposition of type I collagen, the main component of bone extracellular matrix, the time course of gelatinolytic activity expression, the deposition of transforming growth factor beta (TGF-beta), and the ability of cells to differentiate into adipocytes. Our results indicate that cells derived from osteoporotic donors synthesized 50% less type I collagen than normal cells and maintained higher levels of gelatinolytic activity under differentiation conditions (70% versus 15% after 14 days in culture). MSCs derived from osteoporotic women produced 60-65% less TGF-beta and expressed higher adipogenic capacity. We conclude that the capacity of MSCs derived from osteoporotic postmenopausal women to generate and maintain type I collagen-rich extracellular matrix is decreased, favoring their adipogenic differentiation. These observations may explain the decreased mineralization previously observed in these types of cells.
Type II supernovae (SNe) originate from the explosion of hydrogen-rich supergiant massive stars. Their first electromagnetic signature is the shock breakout, a short-lived phenomenon which can last from hours to days depending on the density at shock emergence. We present 26 rising optical light curves of SN II candidates discovered shortly after explosion by the High cadence Transient Survey (HiTS) and derive physical parameters based on hydrodynamical models using a Bayesian approach. We observe a steep rise of a few days in 24 out of 26 SN II candidates, indicating the systematic detection of shock breakouts in a dense circumstellar matter consistent with a mass loss rateṀ > 10 −4 M yr −1 or a dense atmosphere. This implies that the characteristic hour timescale signature of stellar envelope SBOs may be rare in nature and could be delayed into longer-lived circumstellar material shock breakouts in most Type II SNe.With a new generation of large etendue facilities such as iPTF 1 , SkyMapper 2 , Pan-STARRS 3 , KMTNET 4 , ATLAS 5 , DECam 6 , Hyper Suprime-Cam 7 , ZTF 8 or LSST 9 the study of rare and shortlived phenomena in large volumes of the Universe is becoming possible. This allows not only finding new classes of events, but also systematically studying short-lived phases of evolution in known astrophysical phenomena, such as SN explosions. In this work we present 26 rising optical light curves from Type IIP/L 140003.
After injury to periodontal tissues, a sequentially phased healing response is initiated that enables wound closure and partial restoration of tissue structure and function. Wound closure in periodontal tissues involves the tightly regulated coordination of resident cells in epithelial and connective tissue compartments. Multiple cell populations in these compartments synergize their metabolic activities to reestablish a mucosal seal that involves the underlying periodontal connective tissues and the attachment of these tissues to the tooth surface. The formation of an impermeable seal around the circumference of the tooth is of particular significance in oral health since colonization of tooth surfaces by pathogenic biofilms promotes inflammation, which can contribute to periodontal tissue degradation and tooth loss. The reformation of periodontal tissue structures in the healing response centrally involves fibroblasts, which synthesize and organize the collagen fibers that link alveolar bone and gingiva to the cementum covering the tooth root. The synthesis and remodeling of nascent collagen matrices are of fundamental importance for the reestablishment of a functional periodontium and are mediated by diverse, multi-functional fibroblast populations that reside within the connective tissues of gingiva and periodontal ligament. Notably, after gingival wounding, a fibroblast sub-type (myofibroblast) arises, which is centrally involved in collagen synthesis and fibrillar remodeling. While myofibroblasts are not usually seen in healthy, mature connective tissues, their formation is enhanced by wound-healing cytokines. The formation of myofibroblasts is also modulated by the stiffness of the extracellular matrix, which is mechanosensed by resident precursor cells in the gingival connective tissue microenvironment. Here, we consider the cellular origins and the factors that control the differentiation and matrix remodeling functions of periodontal fibroblasts. An improved understanding of the regulation and function of periodontal fibroblasts will be critical for the development of new therapies to optimize the restoration of periodontal structure and function after wounding.
We present the first results of the High Cadence Transient Survey (HiTS), a survey for which the objective is to detect and follow-up optical transients with characteristic timescales from hours to days, especially the earliest hours of supernova (SN) explosions. HiTS uses the Dark Energy Camera and a custom pipeline for image subtraction, candidate filtering and candidate visualization, which runs in real-time to be able to react rapidly to the new transients. We discuss the survey design, the technical challenges associated with the real-time analysis of these large volumes of data and our first results. In our 2013, 2014, and 2015 campaigns, we detected more than 120 young SN candidates, but we did not find a clear signature from the short-lived SN shock breakouts (SBOs) originating after the core collapse of red supergiant stars, which was the initial science aim of this survey. Using the empirical distribution of limiting magnitudes from our observational campaigns, we measured the expected recovery fraction of randomly injected SN light curves, which included SBO optical peaks produced with models from Tominaga et al. (2011) andSari (2010). From this analysis, we cannot rule out the models from Tominaga et al. (2011) under any reasonable distributions of progenitor masses, but we can marginally rule out the brighter and longer-lived SBO models from Nakar & Sari (2010) under our best-guess distribution of progenitor masses. Finally, we highlight the implications of this work for future massive data sets produced by astronomical observatories,such as LSST.
Background:The influence of the stromal microenvironment on the progression of epithelial cancers has been demonstrated. Unravelling the mechanisms by which stromal cells affect epithelial behaviour will contribute in understanding cellular malignancy. It has been proposed that redox environment has a role in the acquisition of malignancy. In this work, we studied the influence of epithelial cells on the stromal redox status and the consequence of this phenomenon on MCF-7 cell motility.Methods:We analysed in a co-culture system, the effect of RMF-EG mammary stromal cells on the migratory capacity of MCF-7 cell line. To test whether the NOX-dependent stromal redox environment influences the epithelial migratory behaviour, we knocked down the expression of NOX4 using siRNA strategy. The effect of TGF-β1 on NOX4 expression and activity was analysed by qPCR, and intracellular ROS production was measured by a fluorescent method.Results:Migration of MCF-7 breast epithelial cells was stimulated when co-cultured with RMF-EG cells. This effect depends on stromal NOX4 expression that, in turn, is enhanced by epithelial soluble factors. Pre-treatment of stromal cells with TGF-β1 enhanced this migratory stimulus by elevating NOX4 expression and intracellular ROS production. TGF-β1 seems to be a major component of the epithelial soluble factors that stimulate NOX4 expression.Conclusions:Our results have identified that an increased stromal oxidative status, mainly provided by an elevated NOX4 expression, is a permissive element in the acquisition of epithelial migratory properties. The capacity of stromal cells to modify their intracellular ROS production, and accordingly, to increase epithelial motility, seems to depend on epithelial soluble factors among which TGF-β1 have a decisive role.
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