33 research outputs found
Quantitative detection of disseminated melanoma cells by trp-1 transcript analysis reveals stochastic distribution of pulmonary metastases
A better understanding of the process of melanoma metastasis is required to underpin the development of novel therapies that will improve patient outcomes. The use of appropriate animal models is indispensable for investigating the mechanisms of melanoma metastasis. However, reliable and practicable quantification of metastases in experimental mice remains a challenge, particularly if the metastatic burden is low. Here, we describe a qRT-PCR-based protocol that employs the melanocytic marker Trp-1 for the sensitive quantification of melanoma metastases in the murine lung. Using this protocol, we were able to detect the presence of as few as 100 disseminated melanoma cells in lung tissue. This allowed us to quantify metastatic burden in a spontaneous syngeneic B16-F10 metastasis model, even in the absence of visible metastases, as well as in the autochthonous Tg(Grm1)/Cyld melanoma model. Importantly, we also observed an uneven distribution of disseminated melanoma cells amongst the five lobes of the murine lung, which varied considerably from animal to animal. Together, our findings demonstrate that the qRT-PCR-based detection of Trp-1 allows the quantification of low pulmonary metastatic burden in both transplantable and autochthonous murine melanoma models, and show that the analysis of lung metastasis in such models needs to take into account the stochastic distribution of metastatic lesions amongst the lung lobes
Spatiotemporally controlled induction of gene expression in vivo allows tracking the fate of tumor cells that traffic through the lymphatics
Sulfated hyaluronic acid inhibits the hyaluronidase CEMIP and regulates the HA metabolism, proliferation and differentiation of fibroblasts
Loss of ASAP1 in the MMTV-PyMT model of luminal breast cancer activates AKT, accelerates tumorigenesis, and promotes metastasis
IER2-induced senescence drives melanoma invasion through osteopontin
Expression of the immediate-early response gene IER2 has been associated with the progression of several types of cancer, but its functional role is poorly understood. We found that increased IER2 expression in human melanoma is associated with shorter overall survival, and subsequently investigated the mechanisms through which IER2 exerts this effect. In experimental melanoma models, sustained expression of IER2 induced senescence in a subset of melanoma cells in a p53/MAPK/AKT-dependent manner. The senescent cells produced a characteristic secretome that included high levels of the extracellular phosphoglycoprotein osteopontin. Nuclear localization of the IER2 protein was critical for both the induction of senescence and osteopontin secretion. Osteopontin secreted by IER2-expressing senescent cells strongly stimulated the migration and invasion of non-senescent melanoma cells. Consistently, we observed coordinate expression of IER2, p53/p21, and osteopontin in primary human melanomas and metastases, highlighting the pathophysiological relevance of IER2-mediated senescence in melanoma progression. Together, our study reveals that sustained IER2 expression drives melanoma invasion and progression through stimulating osteopontin secretion via the stochastic induction of senescence
Id1 and Id3 Are Regulated Through Matrix‐Assisted Autocrine BMP Signaling and Represent Therapeutic Targets in Melanoma
Opuntia in México: Identifying Priority Areas for Conserving Biodiversity in a Multi-Use Landscape
BACKGROUND: México is one of the world's centers of species diversity (richness) for Opuntia cacti. Yet, in spite of their economic and ecological importance, Opuntia species remain poorly studied and protected in México. Many of the species are sparsely but widely distributed across the landscape and are subject to a variety of human uses, so devising implementable conservation plans for them presents formidable difficulties. Multi-criteria analysis can be used to design a spatially coherent conservation area network while permitting sustainable human usage. METHODS AND FINDINGS: Species distribution models were created for 60 Opuntia species using MaxEnt. Targets of representation within conservation area networks were assigned at 100% for the geographically rarest species and 10% for the most common ones. Three different conservation plans were developed to represent the species within these networks using total area, shape, and connectivity as relevant criteria. Multi-criteria analysis and a metaheuristic adaptive tabu search algorithm were used to search for optimal solutions. The plans were built on the existing protected areas of México and prioritized additional areas for management for the persistence of Opuntia species. All plans required around one-third of México's total area to be prioritized for attention for Opuntia conservation, underscoring the implausibility of Opuntia conservation through traditional land reservation. Tabu search turned out to be both computationally tractable and easily implementable for search problems of this kind. CONCLUSIONS: Opuntia conservation in México require the management of large areas of land for multiple uses. The multi-criteria analyses identified priority areas and organized them in large contiguous blocks that can be effectively managed. A high level of connectivity was established among the prioritized areas resulting in the enhancement of possible modes of plant dispersal as well as only a small number of blocks that would be recommended for conservation management
Costs of group-living for a normally solitary forager: Effects of provisioning tourism on southern stingrays Dasyatis americana
Sensorsystem und Herstellungsverfahren sowie Selbsttestverfahren
NOVELTY - The sensor system includes a substrate (15), on which several sensor elements (10) are mounted. The sensor elements each produce electrical signals based on the thermal radiation they receive. A self-test device such as a heating resistor (53) produces heat by which the sensor elements are warmed. DETAILED DESCRIPTION - A method of manufacturing a substrate for the sensor system is also claimed. USE - For infrared radiation detection using, e.g. a thermopile. For use in motor vehicle, in which all sensors are tested when the vehicle is started up. ADVANTAGE - The system operates reliably. DESCRIPTION OF DRAWING(S) - The drawing shows several embodiments of the invention in combination. sensor elements (10); substrate (15); heating resistor (53)
Voting Systems for Environmental Decisions
Voting systems aggregate preferences efficiently and are often used for deciding conservation priorities. Desirable characteristics of voting systems include transitivity, completeness, and Pareto optimality, among others. Voting systems that are common and potentially useful for environmental decision making include simple majority, approval, and preferential voting. Unfortunately, no voting system can guarantee an outcome, while also satisfying a range of very reasonable performance criteria. Furthermore, voting methods may be manipulated by decision makers and strategic voters if they have knowledge of the voting patterns and alliances of others in the voting populations. The difficult properties of voting systems arise in routine decision making when there are multiple criteria and management alternatives. Because each method has flaws, we do not endorse one method. Instead, we urge organizers to be transparent about the properties of proposed voting systems and to offer participants the opportunity to approve the voting system as part of the ground rules for operation of a group