RNA-dependent association with myosin IIA promotes F-actin-guided trafficking of the ELAV-like protein HuR to polysomes

The role of the mRNA-binding protein human antigen R (HuR) in stabilization and translation of AU-rich elements (ARE) containing mRNAs is well established. However, the trafficking of HuR and bound mRNA cargo, which comprises a fundamental requirement for the aforementioned HuR functions is only poorly understood. By administering different cytoskeletal inhibitors, we found that the protein kinase Cδ (PKCδ)-triggered accumulation of cytoplasmic HuR by Angiotensin II (AngII) is an actin-myosin driven process functionally relevant for stabilization of ARE-bearing mRNAs. Furthermore, we show that the AngII-induced recruitment of HuR and its bound mRNA from ribonucleoprotein particles to free and cytoskeleton bound polysomes strongly depended on an intact actomyosin cytoskeleton. In addition, HuR allocation to free and cytoskeletal bound polysomes is highly sensitive toward RNase and PPtase and structurally depends on serine 318 (S318) located within the C-terminal RNA recognition motif (RRM3). Conversely, the trafficking of the phosphomimetic HuRS318D, mimicking HuR phosphorylation at S318 by the PKCδ remained PPtase resistant. Co-immunoprecipitation experiments with truncated HuR proteins revealed that the stimulus-induced association of HuR with myosin IIA is strictly RNA dependent and mediated via the RRM3. Our data implicate a microfilament dependent transport of HuR, which is relevant for stimulus-induced targeting of ARE-bearing mRNAs from translational inactive ribonucleoprotein particles to polysomes

L1 Retrotransposons in Human Cancers

Retrotransposons like L1 are silenced in somatic cells by a variety of mechanisms acting at different levels. Protective mechanisms include DNA methylation and packaging into inactive chromatin to suppress transcription and prevent recombination, potentially supported by cytidine deaminase editing of RNA. Furthermore, DNA strand breaks arising during attempted retrotranspositions ought to activate cellular checkpoints, and L1 activation outside immunoprivileged sites may elicit immune responses. A number of observations indicate that L1 sequences nevertheless become reactivated in human cancer. Prominently, methylation of L1 sequences is diminished in many cancer types and full-length L1 RNAs become detectable, although strong expression is restricted to germ cell cancers. L1 elements have been found to be enriched at sites of illegitimate recombination in many cancers. In theory, lack of L1 repression in cancer might cause transcriptional deregulation, insertional mutations, DNA breaks, and an increased frequency of recombinations, contributing to genome disorganization, expression changes, and chromosomal instability. There is however little evidence that such effects occur at a gross scale in human cancers. Rather, as a rule, L1 repression is only partly alleviated. Unfortunately, many techniques commonly used to investigate genetic and epigenetic alterations in cancer cells are not well suited to detect subtle effects elicited by partial reactivation of retroelements like L1 which are present as abundant, but heterogeneous copies. Therefore, effects of L1 sequences exerted on the local chromatin structure, on the transcriptional regulation of individual genes, and on chromosome fragility need to be more closely investigated in normal and cancer cells

Transactions That Did Not Happen and Their Influence on Prices

This paper studies data from the wholesale fruit and vegetables market in Marseille. We have details of counteroffers to the prices that were proposed by the seller even when no transaction took place. With a simple heoretical model we analyse the evolution of prices during the day and in particular the relation between the final price struck and the proposals of the two parties. Periods with no buyer refusals, of offers or bargaining with no transaction will lead to a revision of the sellerÕs first price. More importantly the sharing of the surplus moves in the buyerÕs favour during the day. These presumptions are then shown to be confirmed by our data set.bargaining, markets

Insights into cancer mechanisms from genomic research on urological cancers

Molecular mechanisms driving cancer development and progression are rarely unique to one cancer type. Rather, recent genomic studies of urological cancers suggest that common mechanisms recur with variations. Examples include alterations in hypoxia response regulation, epigenetic regulator proteins, and signal transduction pathways in renal, prostatic and urothelial carcinomas. Consideration of these variations alongside the common basic cancer mechanisms might be important for the successful development of targeted therapies

A Theoretical and Experimental Study on the Lewis Acid−Base Adducts (P4E3)·(BX3) (E = S, Se; X = Br, I) and (P4Se3)·(NbCl5)

The Lewis acid−base adducts (P4E3)·(BX3) (E = S, Se; X = Br, I) and (P4Se3)·(NbCl5) have been prepared and characterized by Raman, IR, and solid-state 31P MAS NMR spectroscopy. Hybrid density functional calculations (B3LYP) have been carried out for both the apical and the basal (P4E3)·(BX3) (E = S, Se; X = Br, I) adducts. The thermodynamics of all considered species has been discussed. In accordance with solid-state 31P MAS NMR and vibrational data, the X-ray powder diffraction structures of (P4S3)·(BBr3) [monoclinic, space group P21/m (No. 11), a = 8.8854(1) Å, b = 10.6164(2) Å, c = 6.3682(1) Å, β = 108.912(1)°, V = 568.29(2) Å3, Z = 2] and (P4S3)·(BI3) [orthorhombic, space group Pnma (No. 62), a = 12.5039(5) Å, b = 11.3388(5) Å, c = 8.9298(4) Å, V = 1266.09(9) Å3, Z = 4] indicate the formation of an apical P4S3 complex in the reaction of P4S3 with BX3 (X = Br, I). Basal adducts are formed when P4Se3 is used as the donor species. Vibrational assignment for the normal modes of these adducts has been made on the basis of comparison between theoretically obtained and experimentally observed vibrational data

Setting Rules for 2.7 Billion: a (First) Look into Facebook's Norm-Making System; Results of a Pilot Study

Sie regeln, was auf der Plattform Facebook gesagt werden darf und was gelöscht werden muss, und beeinflussen damit, wie 2,7 Milliarden Nutzer miteinander in Kontakt treten können: Facebooks Gemeinschaftsstandards sind ein Beispiel für den großen Einfluss, den Regeln privater Akteure auf die öffentliche Kommunikation haben. In einer Pilotstudie haben Forscher des Leibniz-Instituts für Medienforschung nun erforscht, wie Facebook seine Regeln entwickelt und welche Maßstäbe und Interessen in diesen Prozess einfließen. Matthias C. Kettemann, Forschungsprogrammleiter und Senior Researcher am HBI, hat eine Woche lang als Beobachter an sämtlichen Meetings des Product Policy Teams teilgenommen, das im Hauptquartier von Facebook in Kalifornien für die Entwicklung der Gemeinschaftsstandards verantwortlich ist. Darüber hinaus hat er in ausführlichen Interviews mit den verantwortlichen Personen untersucht, was die Entstehung neuer Regeln und deren Design motiviert und wie Facebook versucht, durch Konsultationen mit gesellschaftlichen Stakeholdern die Legitimität der privaten Normenordnung zu erhöhen. "Über das Entstehen von Gesetzen wissen wir viel, aber über die Entwicklung der selbst auferlegten Regeln, nach denen Facebook etwa Inhalte löscht, wussten wir bisher nichts", so Kettemann. "Das war lange eine Black Box", meint Prof. Dr. Wolfgang Schulz, Direktor des HBI, "in die wir nun Licht bringen konnten"

Practical shape optimization for turbine and compressor blades

The shape optimization of blades is a crucial step within the design cycle of a whole turbomachine. This paper is a report on a joint project between academia and industry leading to an efficient solution software for this problem to be used in the daily work of concerned engineers. The problem description and solution method, characterized as a partially reduced SQP method, as well as numerical results are presented