Multiple tandem splicing silencer elements suppress aberrant splicing within the long exon 26 of the human Apolipoprotein B gene.

ABSTRACT: BACKGROUND: Apolipoprotein B (APOB) is an integral component of the chylomicron and the atherogenic lipoproteins LDL and Lp(a). Exon 26 of the APOB pre-mRNA is unusually long at 7,572 nt and is constitutively spliced. It is also subject to RNA editing in the intestine, which generates a shortened isoform, APOB48, assembled exclusively into chylomicrons. Due to its length, exon 26 contains multiple pseudo splice sites which are not spliced, but which conform to the degenerate splice site consensus. RESULTS: We demonstrate that these pseudo splice sites are repressed by multiple, tandem splicing silencers distributed along the length of exon 26. The distribution of these elements appears to be heterogeneous, with a greater frequency in the middle 4,800 nt of the exon. CONCLUSION: Repression of these splice sites is key to maintaining the integrity of exon 26 during RNA splicing and therefore the correct expression of both isoforms of APOB

Influence of transport and ocean ice extent on biogenic aerosol sulfur in the Arctic atmosphere

The recent decline in sea ice cover in the Arctic Ocean could affect the regional radiative forcing via changes in sea ice-atmosphere exchange of dimethyl sulfide (DMS) and biogenic aerosols formed from its atmospheric oxidation, such as methanesulfonic acid (MSA). This study examines relationships between changes in total sea ice extent north of 70 degrees N and atmospheric MSA measurement at Alert, Nunavut, during 1980-2009; at Barrow, Alaska, during 1997-2008; and at Ny-Alesund, Svalbard, for 1991-2004. During the 1980-1989 and 1990-1997 periods, summer (July-August) and June MSA concentrations at Alert decreased. In general, MSA concentrations increased at all locations since 2000 with respect to 1990 values, specifically during June and summer at Alert and in summer at Barrow and Ny-Alesund. Our results show variability in MSA at all sites is related to changes in the source strengths of DMS, possibly linked to changes in sea ice extent as well as to changes in atmospheric transport patterns. Since 2000, a late spring increase in atmospheric MSA at the three sites coincides with the northward migration of the marginal ice edge zone where high DMS emissions from ocean to atmosphere have previously been reported. Significant negative correlations are found between sea ice extent and MSA concentrations at the three sites during the spring and June. These results suggest that a decrease in seasonal ice cover influencing other mechanisms of DMS production could lead to higher atmospheric MSA concentrations

Trial protocol OPPTIMUM : does progesterone prophylaxis for the prevention of preterm labour improve outcome?

Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome

The pseudogap: friend or foe of high Tc?

Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

An Action-Based Approach to Presence: Foundations and Methods

This chapter presents an action-based approach to presence. It starts by briefly describing the theoretical and empirical foundations of this approach, formalized into three key notions of place/space, action and mediation. In the light of these notions, some common assumptions about presence are then questioned: assuming a neat distinction between virtual and real environments, taking for granted the contours of the mediated environment and considering presence as a purely personal state. Some possible research topics opened up by adopting action as a unit of analysis are illustrated. Finally, a case study on driving as a form of mediated presence is discussed, to provocatively illustrate the flexibility of this approach as a unified framework for presence in digital and physical environment

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Визначення понять «резидент» і «нерезидент»: проблеми теорії і практики

Досліджено практику застосування понять «резидент» та «нерезидент» у як в Україні так і окремих зарубіжних країнах, а також надано авторське бачення щодо визначення даних термінів. Автори статті визначають умови оподаткування операцій з нерезидентами з огляду на існуючі особливості правозастосовної діяльності і вно­сять окремі пропозиції щодо удосконалення процедури адміністрування податків, що стягуються з нерезидентів.Исследована практика применения понятий «резидент» и «нерезидент» как в Украине, так и отдельных зарубежных странах, а также предоставлено авторское виденье относительно определения данных терминов. Авторы статьи определяют условия налогообложения операций с нерезидентами, учитывая существующие особен­ности правоприменительной деятельности, вносят отдельные предложения относи­тельно усовершенствования процедуры администрирования налогов, которые удержи­ваются из нерезидентов.Іn this article practice of application of concepts «resident» and «non­resident» are explored both in Ukraine and some foreign countries, and granted the author’s view on the definition of these terms. The authors of the article determine the term of taxation of operations with non­residents, taking into account the existing features of legal activity and make some suggestions in relation to the improvement of procedure of administration of taxes which are tightened from non­residents

The walkthrough method : an approach to the study of apps

Software applications (apps) are now prevalent in the digital media environment. They are the site of significant sociocultural and economic transformations across many domains, from health and relationships to entertainment and everyday finance. As relatively closed technical systems, apps pose new methodological challenges for sociocultural digital media research. This paper describes a method, grounded in a combination of science and technology studies with cultural studies, through which researchers can perform a critical analysis of a given app. The method involves establishing an app’s environment of expected use by identifying and describing its vision, operating model, and modes of governance. It then deploys a walkthrough technique to systematically and forensically step through the various stages of app registration and entry, everyday use, and discontinuation of use. The walkthrough method establishes a foundational corpus of data upon which can be built a more detailed analysis of an app’s intended purpose, embedded cultural meanings, and implied ideal users and uses. The walkthrough also serves as a foundation for further user-centred research that can identify how users resist these arrangements and appropriate app technology for their own purposes