The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis

A boron-coated CCD camera for direct detection of Ultracold Neutrons (UCN)

A new boron-coated CCD camera is described for direct detection of ultracold neutrons (UCN) through the capture reactions $^{10}$B (n,$\alpha$0$\gamma$)$^7$Li (6%) and $^{10}$B(n,$\alpha$1$\gamma$)$^7$Li (94%). The experiments, which extend earlier works using a boron-coated ZnS:Ag scintillator, are based on direct detections of the neutron-capture byproducts in silicon. The high position resolution, energy resolution and particle ID performance of a scientific CCD allows for observation and identification of all the byproducts $\alpha$, $^7$Li and $\gamma$ (electron recoils). A signal-to-noise improvement on the order of 10$^4$ over the indirect method has been achieved. Sub-pixel position resolution of a few microns is demonstrated. The technology can also be used to build UCN detectors with an area on the order of 1 m$^2$. The combination of micrometer scale spatial resolution, few electrons ionization thresholds and large area paves the way to new research avenues including quantum physics of UCN and high-resolution neutron imaging and spectroscopy.Comment: 10 pages, 8 figure

Kentucky UST Field Manual

This study was undertaken to address the removal and closure of defective petroleum underground storage tanks in Kentucky. Goals for the study included: To address standards for levels of contamination requiring corrective action consistent with accepted scientific and technical principles. To recommend a matrix or scoring system to be used for (a) ranking sites as to actual or potential harm to human health and the environment caused by release of petroleum from a petroleum storage tank, and (2) establishing standards and procedures for corrective action that shall adequately protect human health and the environment. To address all compounds individually and collectively known as petroleum. To produce a report that shall be scientifically defensible

Prediction of Anisotropic Single-Dirac-Cones in Bi1−x{}_{1-x}Sbx{}_{x} Thin Films

The electronic band structures of Bi${}_{1-x}$Sb${}_{x}$ thin films can be varied as a function of temperature, pressure, stoichiometry, film thickness and growth orientation. We here show how different anisotropic single-Dirac-cones can be constructed in a Bi${}_{1-x}$Sb${}_{x}$ thin film for different applications or research purposes. For predicting anisotropic single-Dirac-cones, we have developed an iterative-two-dimensional-two-band model to get a consistent inverse-effective-mass-tensor and band-gap, which can be used in a general two-dimensional system that has a non-parabolic dispersion relation as in a Bi${}_{1-x}$Sb${}_{x}$ thin film system

Status Report: Identification of Appropriate Standards for Corrective Action for a Release from Petroleum Underground Storage Tanks, Volume 1

This study was undertaken to address the removal and closure of defective petroleum underground storage tanks in Kentucky: To address standards for levels of contamination requiring corrective action consistent with accepted scientific and technical principles. To recommend a matrix or scoring system to be used for (a) ranking sites as to actual or potential harm to human health and the environment caused by a release of petroleum from a petroleum storage tank, and (b) establishing standards and procedures for corrective action that shall adequately protect human health and the environment. To address all compounds individually and collectively known as petroleum. To produce a report that shall be scientifically defensible

Quantifying decoherence in continuous variable systems

We present a detailed report on the decoherence of quantum states of continuous variable systems under the action of a quantum optical master equation resulting from the interaction with general Gaussian uncorrelated environments. The rate of decoherence is quantified by relating it to the decay rates of various, complementary measures of the quantum nature of a state, such as the purity, some nonclassicality indicators in phase space and, for two-mode states, entanglement measures and total correlations between the modes. Different sets of physically relevant initial configurations are considered, including one- and two-mode Gaussian states, number states, and coherent superpositions. Our analysis shows that, generally, the use of initially squeezed configurations does not help to preserve the coherence of Gaussian states, whereas it can be effective in protecting coherent superpositions of both number states and Gaussian wave packets.Comment: Review article; 36 pages, 19 figures; typos corrected, references adde

Examples of sequence conservation analyses capture a subset of mouse long non-coding RNAs sharing homology with fish conserved genomic elements

Background: Long non-coding RNAs (lncRNA) are a major class of non-coding RNAs. They are involved in diverse intra-cellular mechanisms like molecular scaffolding, splicing and DNA methylation. Through these mechanisms they are reported to play a role in cellular differentiation and development. They show an enriched expression in the brain where they are implicated in maintaining cellular identity, homeostasis, stress responses and plasticity. Low sequence conservation and lack of functional annotations make it difficult to identify homologs of mammalian lncRNAs in other vertebrates. A computational evaluation of the lncRNAs through systematic conservation analyses of both sequences as well as their genomic architecture is required.Results: Our results show that a subset of mouse candidate lncRNAs could be distinguished from random sequences based on their alignment with zebrafish phastCons elements. Using ROC analyses we were able to define a measure to select significantly conserved lncRNAs. Indeed, starting from ~2,800 mouse lncRNAs we could predict that between 4 and 11% present conserved sequence fragments in fish genomes. Gene ontology (GO) enrichment analyses of protein coding genes, proximal to the region of conservation, in both organisms highlighted similar GO classes like regulation of transcription and central nervous system development. The proximal coding genes in both the species show enrichment of their expression in brain. In summary, we show that interesting genomic regions in zebrafish could be marked based on their sequence homology to a mouse lncRNA, overlap with ESTs and proximity to genes involved in nervous system development.Conclusions: Conservation at the sequence level can identify a subset of putative lncRNA orthologs. The similar protein-coding neighborhood and transcriptional information about the conserved candidates provide support to the hypothesis that they share functional homology. The pipeline herein presented represents a proof of principle showing that a portion between 4 and 11% of lncRNAs retains region of conservation between mammals and fishes. We believe this study will result useful as a reference to analyze the conservation of lncRNAs in newly sequenced genomes and transcriptomes. \uc2\ua9 2013 Basu et al.; licensee BioMed Central Ltd

A Pathway to Precision Medicine for Aboriginal Australians: A Study Protocol

Published: 21 June 2021(1) Background: Genomic precision medicine (PM) utilises people’s genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.Yeu-Yao Cheng, Jack Nunn, John Skinner, Boe Rambaldini, Tiffany Boughtwood, Tom Calma, Alex Brown, Cliff Meldrum, Marcel E. Dinger, Jennifer A. Byrne, Debbie McCowen, Jayden Potter, Kerry Faires, Sandra Cooper and Kylie Gwynn

SEQADAPT: an adaptable system for the tracking, storage and analysis of high throughput sequencing experiments

<p>Abstract</p> <p>Background</p> <p>High throughput sequencing has become an increasingly important tool for biological research. However, the existing software systems for managing and processing these data have not provided the flexible infrastructure that research requires.</p> <p>Results</p> <p>Existing software solutions provide static and well-established algorithms in a restrictive package. However as high throughput sequencing is a rapidly evolving field, such static approaches lack the ability to readily adopt the latest advances and techniques which are often required by researchers. We have used a loosely coupled, service-oriented infrastructure to develop SeqAdapt. This system streamlines data management and allows for rapid integration of novel algorithms. Our approach also allows computational biologists to focus on developing and applying new methods instead of writing boilerplate infrastructure code.</p> <p>Conclusion</p> <p>The system is based around the Addama service architecture and is available at our website as a demonstration web application, an installable single download and as a collection of individual customizable services.</p

Nuclear Organization and Dynamics of 7SK RNA in Regulating Gene Expression

We have identified 7SK RNA to be enriched in nuclear speckles. Knock-down of 7SK results in the mislocalization of nuclear speckle constituents, and the transcriptional up-regulation of a reporter gene locus. 7SK RNA transiently associates with the locus upon transcriptional down-regulation correlating with the displacement of pTEF-b