1,198 research outputs found

    The role of epithelial-to-mesenchymal plasticity in ovarian cancer progression and therapy resistance

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    Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent development of resistance to current chemotherapeutic regimens. Growing evidence demonstrates that apart from its role in ovarian cancer progression, epithelial-to-mesenchymal transition (EMT) can promote chemotherapy resistance. In this review, we will highlight the contribution of EMT to the distinct steps of ovarian cancer progression. In addition, we will review the different types of ovarian cancer resistance to therapy with particular attention to EMT-mediated mechanisms such as cell fate transitions, enhancement of cancer cell survival, and upregulation of genes related to drug resistance. Preclinical studies of anti-EMT therapies have yielded promising results. However, before anti-EMT therapies can be effectively implemented in clinical trials, more research is needed to elucidate the mechanisms leading to EMT-induced therapy resistance

    Melanoma cells revive an embryonic transcriptional network to dictate phenotypic heterogeneity

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    Compared to the overwhelming amount of literature describing how epithelial-to-mesenchymal transition (EMT)-inducing transcription factors orchestrate cellular plasticity in embryogenesis and epithelial cells, the functions of these factors in non-epithelial contexts, such as melanoma, are less clear. Melanoma is an aggressive tumor arising from melanocytes, endowed with unique features of cellular plasticity. The reversible phenotype-switching between differentiated and invasive phenotypes is increasingly appreciated as a mechanism accounting for heterogeneity in melanoma and is driven by oncogenic signaling and environmental cues. This phenotypic switch is coupled with an intriguing and somewhat counterintuitive signaling switch of EMT-inducing transcription factors. In contrast to carcinomas, different EMT-inducing transcription factors have antagonizing effects in melanoma. Balancing between these different EMT transcription factors is likely the key to successful metastatic spread of melanoma

    Parallelism and divergence in immune responses: a comparison of expression levels in two lakes

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    Question: How do immune phenotypes differ between infected and uninfected wild individuals, and is the effect the same in different populations? Organisms: Threespine stickleback (Gasterosteus aculeatus) from two lake populations on the island of North Uist, Scotland, sampled in May 2015. Methods: For each fish, we recorded length, sex, reproductive status, condition, and parasitic infection. We measured the expression levels of eight genes that act as key markers of immune system function using qPCR, and then examined the relationship between measured factors and immune gene expression profiles within each population. Conclusions: Populations differed significantly in their immune gene expression profiles. Within each population, multiple factors, including condition, reproductive status, and Schistocephalus solidus infection levels, were found to correlate with expression levels of different arms of the immune system

    Does operational oceanography address the needs of fisheries and applied environmental scientists?

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    Although many oceanographic data products are now considered operational, continued dialogue between data producers and their user communities is still needed. The fisheries and environmental science communities have often been criticized for their lack of multidisciplinarity, and it is not clear whether recent developments in operational oceanographic products are addressing these needs. The International Council for the Exploration of the Sea (ICES) Working Group on Operational Oceanographic products for Fisheries and Environment (WGOOFE) identified a potential mismatch between user requirements and the perception of requirements by the providers. Through a questionnaire (98 respondents), WGOOFE identified some of these issues. Although products of physical variables were in higher demand, several biological parameters scored in the top 10 rankings. Users placed specific focus on historic time series products with monthly or annual resolution and updating on similar time scales. A significant percentage requested access to numerical data rather than graphical output. While the outcomes of this survey challenge our views of operational oceanography, several initiatives are already attempting to close the gap between user requirements and products available

    Aggregation and structural phase transitions of semiflexible polymer bundles: a braided circuit topology approach

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    We present a braided circuit topology framework for investigating topology and structural phase transitions in aggregates of semiflexible polymers. In the conventional approach to circuit topology, which specifically applies to single isolated folded linear chains, the number and arrangement of contacts within the circuitry of a folded chain give rise to increasingly complex fold topologies. Another avenue for achieving complexity is through the interaction and entanglement of two or more folded linear chains. The braided circuit topology approach describes the topology of such multiple-chain systems and offers topological measures such as writhe, complexity, braid length, and isotopy class. This extension of circuit topology to multichains reveals the interplay between collapse, aggregation, and entanglement. We show that circuit topological motif fractions are ideally suited order parameters to characterise structural phase transitions in entangled systems.Comment: 8 pages, 8 figures + Supplemental Materia

    Decoding chirality in circuit topology of a self entangled chain through braiding

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    Circuit topology employs fundamental units of entanglement, known as soft contacts, for constructing knots from the bottom up, utilising circuit topology relations, namely parallel, series, cross, and concerted relations. In this article, we further develop this approach to facilitate the analysis of chirality, which is a significant quantity in polymer chemistry. To achieve this, we translate the circuit topology approach to knot engineering into a braid-theoretic framework. This enables us to calculate the Jones polynomial for all possible binary combinations of contacts in cross or concerted relations and to show that, for series and parallel relations, the polynomial factorises. Our results demonstrate that the Jones polynomial provides a powerful tool for analysing the chirality of molecular knots constructed using circuit topology. The framework presented here can be used to design and engineer a wide range of entangled chain with desired chiral properties, with potential applications in fields such as materials science and nanotechnology.Comment: 8 pages, 5 figures, 3 table

    The Sub-Polar Gyre Index - a community data set for application in fisheries and environment research

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    Abstract. Scientific interest in the sub-polar gyre of the North Atlantic Ocean has increased in recent years. The sub-polar gyre has contracted and weakened, and changes in circulation pathways have been linked to changes in marine ecosystem productivity. To aid fisheries and environmental scientists, we present here a time series of the Sub-Polar Gyre Index (SPG-I) based on monthly mean maps of sea surface height. The established definition of the SPG-I is applied, and the first EOF (empirical orthogonal function) and PC (principal component) are presented. Sensitivity to the spatial domain and time series length are explored but found not to be important factors in terms of the SPG-I's interpretation. Our time series compares well with indices presented previously. The SPG-I time series is freely available online (http://dx.doi.org/10.7489/1806-1), and we invite the community to access, apply, and publish studies using this index time series. </jats:p

    Combining in situ measurements and altimetry to estimate volume

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    From 1994 to 2011, instruments measuring ocean currents (Acoustic Doppler Current Profilers; ADCPs) have been moored on a section crossing the Faroe–Shetland Channel. Together with CTD (Conductivity Temperature Depth) measurements from regular research vessel occupations, they describe the flow field and water mass structure in the channel. Here, we use these data to calculate the average volume transport and properties of the flow of warm water through the channel from the Atlantic towards the Arctic, termed the Atlantic inflow. We find the average volume transport of this flow to be 2.7 ± 0.5 Sv (1 Sv = 106 m3 s–1) between the shelf edge on the Faroe side and the 150 m isobath on the Shetland side. The average heat transport (relative to 0 °C) was estimated to be 107 ± 21 TW (1 TW = 1012 W) and the average salt import to be 98 ± 20 × 106 kg s−1. Transport values for individual months, based on the ADCP data, include a large level of variability, but can be used to calibrate sea level height data from satellite altimetry. In this way, a time series of volume transport has been generated back to the beginning of satellite altimetry in December 1992. The Atlantic inflow has a seasonal variation in volume transport that peaks around the turn of the year and has an amplitude of 0.7 Sv. The Atlantic inflow has become warmer and more saline since 1994, but no equivalent trend in volume transport was observed
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