Genome-Wide Profiling Identified a Set of miRNAs that Are Differentially Expressed in Glioblastoma Stem Cells and Normal Neural Stem Cells

A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells

Attenuation of Vaccinia Tian Tan Strain by Removal of Viral TC7L-TK2L and TA35R Genes

Vaccinia Tian Tan (VTT) was attenuated by deletion of the TC7L-TK2L and TA35R genes to generate MVTT3. The mutant was generated by replacing the open reading frames by a gene encoding enhanced green fluorescent protein (EGFP) flanked by loxP sites. Viruses expressing EGFP were then screened for and purified by serial plaque formation. In a second step the marker EGFP gene was removed by transfecting cells with a plasmid encoding cre recombinase and selecting for viruses that had lost the EGFP phenotype. The MVTT3 mutant was shown to be avirulent and immunogenic. These results support the conclusion that TC7L-TK2L and TA35R deletion mutants can be used as safe viral vectors or as platform for vaccines

Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo

Background: A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions. Methodology and Principal Findings: We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells. Conclusion: Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies

The serious games ecosystem: Interdisciplinary and intercontextual praxis

This chapter will situate academia in relation to serious games commercial production and contextual adoption, and vice-versa. As a researcher it is critical to recognize that academic research of serious games does not occur in a vaccum. Direct partnerships between universities and commercial organizations are increasingly common, as well as between research institutes and the contexts that their serious games are deployed in. Commercial production of serious games and their increased adoption in non-commercial contexts will influence academic research through emerging impact pathways and funding opportunities. Adding further complexity is the emergence of commercial organizations that undertake their own research, and research institutes that have inhouse commercial arms. To conclude, we explore how these issues affect the individual researcher, and offer considerations for future academic and industry serious games projects

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Efficient improvement for dissociation behavior and thermal decomposition of manganese ore by microwave calcination

Abstract Traditional smelting process of manganese ore was plagued with high consume of power and coke, and spraying and slag turning accidents caused by violent decomposition of carbonates and manganese oxides in manganese ore. In the present work, the thermal decomposition mechanism and phase structures of manganese ore were systematically investigated, calcined through microwave calcination approach and characterized by XRD, SEM and EDAX. Results indicated that microwave calcination had a significantly better effect than conventional calcination for manganese ore. An increase in calcination temperature was found to present a more profound effect than calcination duration. The optimum calcination temperature was identified to be 950 °C, with the calcination duration being 30 min, and manganese ore grade increased from initial 30% to 39%–42%, with the pulverization ratio being 8%–9%. Peak intensities of Mn3O4 phase enhanced with calcination temperature increasing, and irregular cracks and pits appeared on the surface of the microwave calcined manganese ore. Meanwhile, the feasibility of decomposition reactions of manganese ore at the considered temperature regime was confirmed by thermodynamics analysis. The upgrading and modified manganese ore by microwave calcination can realize the direct smelting of the concentrate. The work proposes an efficient calcination idea for manganese ore by microwave calcination

Dielectric properties and thermal behavior of electrolytic manganese anode mud in microwave field

Abstract Exploring the dielectric properties of a material can provide guidance for applications of microwave technology to the material. In this work, dielectric properties and thermal behavior of manganese anode mud and pure MnO₂, CaSO₄ and PbSO₄ components were systematically investigated. Results indicated that manganese anode mud showed excellent responsiveness to microwaves, with εr′ value of 17.971 (F/M) at room temperature and a maximum value of 20.816 (F/M) at 150 °C, rendering it took only 5.5 min for manganese anode mud to be heated from room temperature to 1000 °C. The dielectric properties of manganese anode mud were related to its thermal behavior, mainly affected by MnO₂ component. Moreover, the heating process of manganese anode mud was divided into four stages identified by temperatures: less than 200 °C, 200 °C–700 °C, 700 °C–900 °C, greater than 900 °C, corresponding to the five stages of thermal behavior: the removal of absorption water and combined water, the decomposition reaction of Pb₂Mn₈O16, and the deoxidation reactions of PbO₂, MnO₂ and Mn3O₄. The work highlights the feasibility of processing manganese anode mud by microwave heating

One-step preparation of CaO-doped partially stabilized zirconia from fused zirconia

Abstract Partially stabilized zirconia (PSZ) replaces the widespread applications of full stabilized zirconia (FSZ) on ceramics materials and refractories materials, attributed to its excellent properties including small coefficient of thermal expansion, low thermal conductivity and good thermal shock resistance. In this work, CaO-doped partially stabilized zirconia (CaO-PSZ) was optimizedly prepared from fused zirconia through conventional roasting. Meanwhile, the effects of roasting temperature and duration time on stability properties were explored to determine the stability parameters of the prepared CaO-PSZ. Results indicated that the zirconia stability rate synchronously improved with the decrease of roasting temperature and duration time, which was attributed to that the martensitic transformation of fused zirconia with volume change plays a toughening effect, further rendering the change of zirconia stability properties. XRD patterns verified the martensitic transformation, representing by cubic ZrO₂ phase (c-ZrO₂) in raw fused zirconia was partially transformed into monoclinic ZrO₂ phase (m-ZrO₂) at 1450 °C for 4 h. Moreover, the phase transition law of fused zirconia was revealed through SEM and EDAX characterization for the raw fused zirconia and the prepared CaO-PSZ. SEM patterns showed acicular patterns of grains and round fine particles clustered at grain boundaries, indicating that CaO stabilizer precipitated on grain boundaries and rendered the crystal structure enhanced, which the result was consistent with EDAX analysis. This work can lay a significant foundation for applications of microwave heating on the preparation of partially stabilized zirconia (PSZ) from fused zirconia