On the determinants of external imbalances and net international portfolio flows: a global perspective

In a panel covering a large number of countries from 1970 to 2003, we show that net portfolio flows play an important role in correcting external imbalances, since they are driven by common determinants represented by countries’ demographic profiles, the quality of institutions, monetary aggregates and initial net financial asset positions. Population ageing causes current account deficits, net equity inflows and net outflows in debt instruments. A higher money to GDP ratio – associated with lower interest rates – favours international investments in domestic stocks to the detriment of the less attractive domestic bonds. Additionally, current account balances are driven negatively by real GDP growth, losses in competitiveness and increases in the quality of the institutions; net equity flows are driven positively by the quality of the institutions and negatively by per capita income; while net flows in debt instruments are driven by long-term interest rate differentials and deviations from the UIP. JEL Classification: F21, F32, F41, O16Current accounts, net portfolio flows, panel regressions

Molecular architecture of Zinc chelating small molecules that inhibit spliceosome assembly at an early stage.

The removal of intervening sequences (introns) from a primary RNA transcript is catalyzed by the spliceosome, a large ribonucleoprotein complex. At the start of each splicing cycle, the spliceosome assembles anew in a sequentially ordered manner on the pre-mRNA intron to be removed. We describe here the identification of a series of naphthalen-2-yl hydroxamate compounds that inhibit pre-mRNA splicing in vitro with mid- to high-micromolar values of IC50. These hydroxamates stall spliceosome assembly at the A complex stage. A structure-activity analysis of lead compounds revealed three pharmacophores that are essential for splicing inhibition. Specifically, a hydroxamate as a zinc-binding group and a 6-methoxynaphthalene cap group are both critical, and a linker chain comprising eight to nine methylene groups is also important, for the specific binding to the docking site of a target protein molecule and precise positioning of the zinc binding group. As we found no correlation between the inhibition patterns of known histone deacetylases on the one hand and pre-mRNA splicing on the other, we conclude that these compounds may function through the inhibition of the activities of other, at present, unknown spliceosome-associated zinc metalloprotein(s)

SANS (USH1G) regulates pre-mRNA splicing by mediating the intra-nuclear transfer of tri-snRNP complexes

Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofactor SON but also with PRPFs and snRNAs related to the tri-snRNP complex. SANS is required for the transfer of tri-snRNPs between Cajal bodies and nuclear speckles for spliceosome assembly and may also participate in snRNP recycling back to Cajal bodies. SANS depletion alters the kinetics of spliceosome assembly, leading to accumulation of complex A. SANS deficiency and USH1G pathogenic mutations affects splicing of genes related to cell proliferation and human Usher syndrome. Thus, we provide the first evidence that splicing dysregulation may participate in the pathophysiology of Usher syndrome

Satisfying needs through food and drink

Essen ist nicht nur Voraussetzung für das Überleben, es dient darüber hinaus auch weiterengrundlegenden psychischen und sozialen Bedürfnissen. Die Steuerung von Hunger und Sättigung erfolgt daher sowohl über die Homöostase als auch durch psychische und soziale Faktoren, die ebenso Einfluss auf die cerebrale Steuerung nehmen. Eine Aufgabe der Ernährungs- und Verbraucherbildung ist, auf der Basis von Wissen über diese Zusammenhänge Essverhalten verstehen, reflektieren und gestalten zu können. (DIPF/Orig.)Food is not only a prerequisite for survival, but it also serves other basic psychological and social needs. The control of hunger and satiety is therefore affected both through homeostasis and through psychological and social factors that also influence cerebral control. One task of nutrition and consumer education is to understand, reflect, and shape eating behaviour based on knowledge about these interrelationships. (DIPF/Orig.

Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Dynamic Regulation of Alternative Splicing by Silencers that Modulate 5′ Splice Site Competition

SummaryAlternative splicing makes a major contribution to proteomic diversity in higher eukaryotes with ∼70% of genes encoding two or more isoforms. In most cases, the molecular mechanisms responsible for splice site choice remain poorly understood. Here, we used a randomization-selection approach in vitro to identify sequence elements that could silence a proximal strong 5′ splice site located downstream of a weakened 5′ splice site. We recovered two exonic and four intronic motifs that effectively silenced the proximal 5′ splice site both in vitro and in vivo. Surprisingly, silencing was only observed in the presence of the competing upstream 5′ splice site. Biochemical evidence strongly suggests that the silencing motifs function by altering the U1 snRNP/5′ splice site complex in a manner that impairs commitment to specific splice site pairing. The data indicate that perturbations of non-rate-limiting step(s) in splicing can lead to dramatic shifts in splice site choice

Professional training in nutrition education. Participants and implementation framework in primary school

Non-formale Fortbildungsangebote für die Ernährungspraxis werden zunehmend angeboten und in Anspruch genommen. In der vorliegenden Untersuchung wurden die Teilnehmenden eines bundesweiten Fortbildungsangebots, die Ernährungspraxis in der Grundschule aufgreifen möchten, hinsichtlich ihrer Qualifikation und Kompetenzen sowie den jeweiligen Rahmenbedingungen ihrer Tätigkeit in der Grundschule untersucht. (DIPF/Orig.)Non-formal professional training opportunities in nutrition education are increasingly being offered and taken up. The present study examined the participants in a nationwide non-formal training in nutrition education, who are interested in taking up nutritional education into primary schools, with regard to their qualifications, competencies and implementation framework. (DIPF/Orig.

Equation of State of Nuclear Matter at high baryon density

A central issue in the theory of astrophysical compact objects and heavy ion reactions at intermediate and relativistic energies is the Nuclear Equation of State (EoS). On one hand, the large and expanding set of experimental and observational data is expected to constrain the behaviour of the nuclear EoS, especially at density above saturation, where it is directly linked to fundamental processes which can occur in dense matter. On the other hand, theoretical predictions for the EoS at high density can be challenged by the phenomenological findings. In this topical review paper we present the many-body theory of nuclear matter as developed along different years and with different methods. Only nucleonic degrees of freedom are considered. We compare the different methods at formal level, as well as the final EoS calculated within each one of the considered many-body schemes. The outcome of this analysis should help in restricting the uncertainty of the theoretical predictions for the nuclear EoS.Comment: 51 pages, to appear in J. Phys. G as Topical Revie