The changing paradigm of intron retention: regulation, ramifications and recipes

Intron retention (IR) is a form of alternative splicing that has long been neglected in mammalian systems although it has been studied for decades in non-mammalian species such as plants, fungi, insects and viruses. It was generally assumed that mis-splicing, leading to the retention of introns, would have no physiological consequence other than reducing gene expression by nonsense-mediated decay. Relatively recent landmark discoveries have highlighted the pivotal role that IR serves in normal and disease-related human biology. Significant technical hurdles have been overcome, thereby enabling the robust detection and quantification of IR. Still, relatively little is known about the cis- and trans-acting modulators controlling this phenomenon. The fate of an intron to be, or not to be, retained in the mature transcript is the direct result of the influence exerted by numerous intrinsic and extrinsic factors at multiple levels of regulation. These factors have altered current biological paradigms and provided unexpected insights into the transcriptional landscape. In this review, we discuss the regulators of IR and methods to identify them. Our focus is primarily on mammals, however, we broaden the scope to non-mammalian organisms in which IR has been shown to be biologically relevant

Preparation of uranium standard solutions for x-ray fluorescence analysis

A method has been developed for gravimetrically preparing uranium nitrate standards with an estimated mean error of 0.1% (1 sigma) and a maximum error of 0.2% (1 sigma) for the total uranium weight. Two source materials, depleted uranium dioxide powder and NBS Standard Reference Material 960 uranium metal, were used to prepare stock solutions. The NBS metal proved to be superior because of the small but inherent uncertainty in the stoichiometry of the uranium oxide. These solutions were used to prepare standards in a freeze-dried configuration suitable for x-ray fluorescence analysis. Both gravimetric and freeze-drying techniques are presented. Volumetric preparation was found to be unsatisfactory for 0.1% precision for the sample size of interest. One of the primary considerations in preparing uranium standards for x-ray fluorescence analysis is the development of a technique for dispensing a 50-..mu..l aliquot of a standard solution with a precision of 0.1% and an accuracy of 0.1%. The method developed corrects for variation in aliquoting and for evaporation loss during weighing. Two sets, each containing 50 standards have been produced. One set has been retained by LLL and one set retained by the Savannah River project (SRP)

Nuclear shell-model calculations for 6Li and 14N with different NN potentials

Two ``phase-shift equivalent'' local NN potentials with different parametrizations, Reid93 and NijmII, which were found to give nearly identical results for the triton by Friar et al, are shown to yield remarkably similar results for 6Li and 14N in a (0+2)hw no-core space shell-model calculation. The results are compared with those for the widely used Hamada-Johnson hard-core and the original Reid soft-core potentials, which have larger deuteron D-state percentages. The strong correlation between the tensor strength and the nuclear binding energy is confirmed. However, many nuclear-structure properties seem to be rather insensitive to the details of the NN potential and, therefore, cannot be used to test various NN potentials. (Submitted to Phys. Rev. C on Nov. 9, 1993 as a Brief Report.)Comment: 12 text pages and 1 figure (Figure available upon request), University of Arizona Physics Preprint (Number not yet assigned

Multibeam Maser Survey of methanol and excited OH in the Magellanic clouds: new detections and maser abundance estimates

‘The definitive version is available at www.blackwell-synergy.com.’ Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.12888.xPeer reviewe

Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner

CTCF is a master regulator of gene transcription and chromatin organisation with occupancy at thousands of DNA target sites genome-wide. While CTCF is essential for cell survival, CTCF haploinsufficiency is associated with tumour development and hypermethylation. Increasing evidence demonstrates CTCF as a key player in several mechanisms regulating alternative splicing (AS), however, the genome-wide impact of Ctcf dosage on AS has not been investigated. We examined the effect of Ctcf haploinsufficiency on gene expression and AS in five tissues from Ctcf hemizygous (Ctcf+/-) mice. Reduced Ctcf levels caused distinct tissue-specific differences in gene expression and AS in all tissues. An increase in intron retention (IR) was observed in Ctcf+/- liver and kidney. In liver, this specifically impacted genes associated with cytoskeletal organisation, splicing and metabolism. Strikingly, most differentially retained introns were short, with a high GC content and enriched in Ctcf binding sites in their proximal upstream genomic region. This study provides new insights into the effects of CTCF haploinsufficiency on organ transcriptomes and the role of CTCF in AS regulation

Radio-Continuum study of the Nearby Sculptor Group Galaxies. Part 1: NGC 300 at lambda = 20 cm

A series of new radio-continuum (lambda=20 cm) mosaic images focused on the NGC 300 galactic system were produced using archived observational data from the VLA and/or ATCA. These new images are both very sensitive (rms=60 microJy) and feature high angular resolution (<10"). The most prominent new feature is the galaxy's extended radio-continuum emission, which does not match its optical appearance. Using these newly created images a number of previously unidentified discrete sources have been discovered. Furthermore, we demonstrate that a joint deconvolution approach to imaging this complete data-set is inferior when compared to an immerge approach.Comment: 13 pages, 12 figures, accepted to APSS, new version to correct the missing reference

Dual-Composite Right-Left Handed Transmission Lines for the Design of Compact Diplexers

In this study, the use of dual-composite right-left-handed (D-CRLH) transmission lines is proposed for the design of diplexers. The D-CRLH diplexers present advantages over conventional diplexers such as smaller size (especially in the ultra high frequency band). The design procedure and the design equations are presented in this paper. The non-linear phase response of a D-CRLH transmission line has been used to design diplexers at any arbitrary frequencies. Finally, two diplexers have been designed and manufactured: one for quite near frequencies and the other for further ones. The simulation results show good agreement with the measurements. A sensitivity analysis has been provided to show the robustness of this kind of circuits

An analysis of the FIR/RADIO Continuum Correlation in the Small Magellanic Cloud

The local correlation between far-infrared (FIR) emission and radio-continuum (RC) emission for the Small Magellanic Cloud (SMC) is investigated over scales from 3 kpc to 0.01 kpc. Here, we report good FIR/RC correlation down to ~15 pc. The reciprocal slope of the FIR/RC emission correlation (RC/FIR) in the SMC is shown to be greatest in the most active star forming regions with a power law slope of ~1.14 indicating that the RC emission increases faster than the FIR emission. The slope of the other regions and the SMC are much flatter and in the range of 0.63-0.85. The slopes tend to follow the thermal fractions of the regions which range from 0.5 to 0.95. The thermal fraction of the RC emission alone can provide the expected FIR/RC correlation. The results are consistent with a common source for ultraviolet (UV) photons heating dust and Cosmic Ray electrons (CRe-s) diffusing away from the star forming regions. Since the CRe-s appear to escape the SMC so readily, the results here may not provide support for coupling between the local gas density and the magnetic field intensity.Comment: 19 pages, 7 Figure

An explicit formula for the coefficients in Laplace's method

Laplace's method is one of the fundamental techniques in the asymptotic approximation of integrals. The coefficients appearing in the resulting asymptotic expansion, arise as the coefficients of a convergent or asymptotic series of a function defined in an implicit form. Due to the tedious computation of these coefficients, most standard textbooks on asymptotic approximations of integrals do not give explicit formulas for them. Nevertheless, we can find some more or less explicit representations for the coefficients in the literature: Perron's formula gives them in terms of derivatives of an explicit function; Campbell, Fr\"oman and Walles simplified Perron's method by computing these derivatives using an explicit recurrence relation. The most recent contribution is due to Wojdylo, who rediscovered the Campbell, Fr\"oman and Walles formula and rewrote it in terms of partial ordinary Bell polynomials. In this paper, we provide an alternative representation for the coefficients, which contains ordinary potential polynomials. The proof is based on Perron's formula and a theorem of Comtet. The asymptotic expansions of the gamma function and the incomplete gamma function are given as illustrations.Comment: 14 pages, to appear in Constructive Approximatio

PROTOCOL: Methods used in the development, production and updating of evidence and gap maps: a scoping review

Evidence and gap maps (EGMs) are an increasinly popular approach used in evidence synthesis. As an approach they address broad research questions, describing the existing evidence base, highlighting evidence gaps and providing an interactive visual tool for knowledge users. The purpose of this methodological study is to explore the the processes used in the development of EGM's and how they are reported. The aim is to better understand current practice and identify where clearer guidance is needed to support their production