Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression

BACKGROUND: Screening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups. METHODS: The expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues. RESULTS: High levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed. CONCLUSION: We identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1327-5) contains supplementary material, which is available to authorized users

Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients

<p>Abstract</p> <p>Background</p> <p>Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA) regulation in two populations of malignant Embryonal Carcinoma (EC) stem cell, which differentiate (NTera2) or remain undifferentiated (2102Ep) during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC) patient samples.</p> <p>Methods</p> <p>miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR.</p> <p>Results</p> <p>Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples.</p> <p>Conclusion</p> <p>miRNA biosynthesis and expression of mature miRNAs, particularly the miR-17/92 family and those clustering to chromosomes 14 and 19, are highly regulated in both progenitor cells and tumour samples. Strikingly, 2102Ep cells are not simply malfunctioning but respond to differentiation specifically, a mechanism that is highly relevant to OSC samples. Our identification and future manipulation of these miRNAs may facilitate generation of lower grade malignancies from these high-grade cells.</p

Root Structure and Growth in Diverse Soils

Unlike most biofuel species, Jatropha curcas has promise for use in marginal lands, but it may serve an additional role by stabilizing soils. We evaluated the growth and structural responsiveness of young J. curcas plants to diverse soil conditions. Soils included a sand, a sandy-loam, and a clay-loam from eastern Mexico. Growth and structural parameters were analyzed for shoots and roots, although the focus was the plasticity of the primary root system architecture (the taproot and four lateral roots). The sandy soil reduced the growth of both shoot and root systems significantly more than sandy-loam or clay-loam soils; there was particularly high plasticity in root and shoot thickness, as well as shoot length. However, the architecture of the primary root system did not vary with soil type; the departure of the primary root system from an index of perfect symmetry was 14 ± 5% (mean ± standard deviation). Although J. curcas developed more extensively in the sandy-loam and clay-loam soils than in sandy soil, it maintained a consistent root to shoot ratio and root system architecture across all types of soil. This strong genetic determination would make the species useful for soil stabilization purposes, even while being cultivated primarily for seed oil

Current State of Microplastic Pollution Research Data: Trends in Availability and Sources of Open Data

The rapid growth in microplastic pollution research is influencing funding priorities, environmental policy, and public perceptions of risks to water quality and environmental and human health. Ensuring that environmental microplastics research data are findable, accessible, interoperable, and reusable (FAIR) is essential to inform policy and mitigation strategies. We present a bibliographic analysis of data sharing practices in the environmental microplastics research community, highlighting the state of openness of microplastics data. A stratified (by year) random subset of 785 of 6,608 microplastics articles indexed in Web of Science indicates that, since 2006, less than a third (28.5%) contained a data sharing statement. These statements further show that most often, the data were provided in the articles’ supplementary material (38.8%) and only 13.8% via a data repository. Of the 279 microplastics datasets found in online data repositories, 20.4% presented only metadata with access to the data requiring additional approval. Although increasing, the rate of microplastic data sharing still lags behind that of publication of peer-reviewed articles on environmental microplastics. About a quarter of the repository data originated from North America (12.8%) and Europe (13.4%). Marine and estuarine environments are the most frequently sampled systems (26.2%); sediments (18.8%) and water (15.3%) are the predominant media. Of the available datasets accessible, 15.4% and 18.2% do not have adequate metadata to determine the sampling location and media type, respectively. We discuss five recommendations to strengthen data sharing practices in the environmental microplastic research community

Assessing recovery from acidification of European surface waters in the year 2010: evaluation of projections made with the MAGIC model in 1995

In 1999 we used the MAGIC (Model of Acidification of Groundwater In Catchments) model to project acidification of acid-sensitive European surface waters in the year 2010, given implementation of the Gothenburg Protocol to the Convention on Long-Range Transboundary Air Pollution (LRTAP). A total of 202 sites in 10 regions in Europe were studied. These forecasts can now be compared with measurements for the year 2010, to give a “ground truth” evaluation of the model. The prerequisite for this test is that the actual sulfur and nitrogen deposition decreased from 1995 to 2010 by the same amount as that used to drive the model forecasts; this was largely the case for sulfur, but less so for nitrogen, and the simulated surface water [NO3–] reflected this difference. For most of the sites, predicted surface water recovery from acidification for the year 2010 is very close to the actual recovery observed from measured data, as recovery is predominantly driven by reductions in sulfur deposition. Overall these results show that MAGIC successfully predicts future water chemistry given known changes in acid deposition

Epitaxial growth of perovskite oxide films facilitated by oxygen vacancies

The authors would like to thank P. Yudin for valuable discussions, N. Nepomniashchaia for VASE studies, and S. Cichon for XPS analysis. The authors acknowledge support from the Czech Science Foundation (Grant No. 19-09671S), the European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem (E. K. and L. R.). Calculations have been done on the LASC Cluster in the ISSP UL.Single-crystal epitaxial films of technologically important and scientifically intriguing multifunctional ABO3 perovskite-type metal oxides are essential for advanced applications and understanding of these materials. In such films, a film-substrate misfit strain enables unprecedented crystal phases and unique properties that are not available in their bulk counterparts. However, the prerequisite growth of strained epitaxial films is fundamentally restricted by misfit relaxation. Here we demonstrate that introduction of a small oxygen deficiency concurrently stabilizes epitaxy and increases lattice strain in thin films of archetypal perovskite oxide SrTiO3. By combining experimental and theoretical methods, we found that lattice distortions around oxygen vacancies lead to anisotropic local stresses, which interact with the misfit strain in epitaxial films. Consequently, specific crystallographic alignments of the stresses are energetically favorable and can facilitate epitaxial growth of strained films. Because anisotropic oxygen-vacancy stresses are inherent to perovskite-type and many other oxides, we anticipate that the disclosed phenomenon of epitaxial stabilization by oxygen vacancies is relevant for a very broad range of functional oxides.This work is licensed under CC BY, CC BY-NC licenses.Czech Science Foundation (Grant No. 19-09671S); European Structural and Investment Funds and the Ministry of Education, Youth and Sports of the Czech Republic through Programme ‘‘Research, Development and Education’’ (Project No. SOLID21 CZ.02.1.01/0.0/0.0/16-019/0000760), and ERA NET project Sun2Chem; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²

Finding the needle in the haystack: why high-throughput screening is good for your health

High-throughput screening is an essential component of the toolbox of modern technologies that improve speed and efficiency in contemporary cancer drug development. This is particularly important as we seek to exploit, for maximum therapeutic benefit, the large number of new molecular targets emerging from the Human Genome Project and cancer genomics. Screening of diverse collections of low molecular weight compounds plays a key role in providing chemical starting points for iterative optimisation by medicinal chemistry. Examples of successful drug discovery programmes based on high-throughput screening are described, and these offer potential in the treatment of breast cancer and other malignancies

Implementing efficient concerted rotations using Mathematica and C code

In this article we demonstrate a general and efficient metaprogramming implementation of concerted rotations using Mathematica. Concerted rotations allow the movement of a fixed portion of a polymer backbone with fixed bending angles, like a protein, while maintaining the correct geometry of the backbone and the initial and final points of the portion fixed. Our implementation uses Mathematica to generate a C code which is then wrapped in a library by a Python script. The user can modify the Mathematica notebook to generate a set of concerted rotations suited for a particular backbone geometry, without having to write the C code himself. The resulting code is highly optimized, performing on the order of thousands of operations per second