Intranasal vitamin B12 administration in elderly patients: A randomized controlled comparison of two dosage regimens

Aim: Vitamin B12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B12 dosage regimens in elderly vitamin B12-deficient patients. Methods: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 μg cobalamin. Total vitamin B12, holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90. Results: Both dosage regimens resulted in a rapid increase of vitamin B12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B12 of 1090 pmol/L (reference 350-650 pmol/L) concentration after 14 days. Following weekly administration, B12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B12 of 717 pmol/L after 90 days. Conclusions: Intranasal vitamin B12 administration is an effective and suitable way to replenish and sustain vitamin B12 levels in elderly patients

Transition from damage to fragmentation in collision of solids

We investigate fracture and fragmentation of solids due to impact at low energies using a two-dimensional dynamical model of granular solids. Simulating collisions of two solid discs we show that, depending on the initial energy, the outcome of a collision process can be classified into two states: a damaged and a fragmented state with a sharp transition in between. We give numerical evidence that the transition point between the two states behaves as a critical point, and we discuss the possible mechanism of the transition.Comment: Revtex, 12 figures included. accepted by Phys. Rev.

Dilatancy transition in a granular model

We introduce a model of granular matter and use a stress ensemble to analyze shearing. Monte Carlo simulation shows the model to exhibit a second order phase transition, associated with the onset of dilatancy.Comment: Future versions can be obtained from: http://www.ma.utexas.edu/users/radin/papers/shear2.pd

Long-term health-related quality of life in young childhood cancer survivors and their parents

Purpose: Few studies have investigated the health-related quality of life (HRQoL) of young childhood cancer survivors and their parents. This study describes parent and child cancer survivor HRQoL compared to population norms and identifies factors influencing child and parent HRQoL. Methods: We recruited parents of survivors who were currently 5 years postdiagnosis. Parents reported on their child's HRQoL (Kidscreen-10), and their own HRQoL (EQ-5D-5L). Parents rated their resilience and fear of cancer recurrence and listed their child's cancer-related late effects. Results: One hundred eighty-two parents of survivors (mean age = 12.4 years old and 9.7 years postdiagnosis) participated. Parent-reported child HRQoL was significantly lower than population norms (48.4 vs. 50.7, p <.009). Parents most commonly reported that their child experienced sadness and loneliness (18.1%). Experiencing more late effects and receiving treatments other than surgery were associated with worse child HRQoL. Parents’ average HRQoL was high (0.90) and no different to population norms. However 38.5% of parents reported HRQoL that was clinically meaningfully different from perfect health, and parents experienced more problems with anxiety/depression (43.4%) than population norms (24.7%, p <.0001). Worse child HRQoL, lower parent resilience, and higher fear of recurrence was associated with worse parent HRQoL. Conclusions: Parents report that young survivors experience small but significant ongoing reductions in HRQoL. While overall mean levels of HRQoL were no different to population norms, a subset of parents reported HRQoL that was clinically meaningfully different from perfect health. Managing young survivors’ late effects and improving parents’ resilience through survivorship may improve HRQoL in long-term survivorship

Analyses of In Vivo Interaction and Mobility of Two Spliceosomal Proteins Using FRAP and BiFC

U1-70K, a U1 snRNP-specific protein, and serine/arginine-rich (SR) proteins are components of the spliceosome and play critical roles in both constitutive and alternative pre-mRNA splicing. However, the mobility properties of U1-70K, its in vivo interaction with SR proteins, and the mobility of the U1-70K-SR protein complex have not been studied in any system. Here, we studied the in vivo interaction of U1-70K with an SR protein (SR45) and the mobility of the U1-70K/SR protein complex using bimolecular fluorescence complementation (BiFC) and fluorescence recovery after photobleaching (FRAP). Our results show that U1-70K exchanges between speckles and the nucleoplasmic pool very rapidly and that this exchange is sensitive to ongoing transcription and phosphorylation. BiFC analyses showed that U1-70K and SR45 interacted primarily in speckles and that this interaction is mediated by the RS1 or RS2 domain of SR45. FRAP analyses showed considerably slower recovery of the SR45/U1-70K complex than either protein alone indicating that SR45/U1-70K complexes remain in the speckles for a longer duration. Furthermore, FRAP analyses with SR45/U1-70K complex in the presence of inhibitors of phosphorylation did not reveal any significant change compared to control cells, suggesting that the mobility of the complex is not affected by the status of protein phosphorylation. These results indicate that U1-70K, like SR splicing factors, moves rapidly in the nucleus ensuring its availability at various sites of splicing. Furthermore, although it appears that U1-70K moves by diffusion its mobility is regulated by phosphorylation and transcription

Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1

Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2). LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA processing and Polycomb regulation

Nucleo-cytoplasmic transport of proteins and RNA in plants

Merkle T. Nucleo-cytoplasmic transport of proteins and RNA in plants. Plant Cell Reports. 2011;30(2):153-176.Transport of macromolecules between the nucleus and the cytoplasm is an essential necessity in eukaryotic cells, since the nuclear envelope separates transcription from translation. In the past few years, an increasing number of components of the plant nuclear transport machinery have been characterised. This progress, although far from being completed, confirmed that the general characteristics of nuclear transport are conserved between plants and other organisms. However, plant-specific components were also identified. Interestingly, several mutants in genes encoding components of the plant nuclear transport machinery were investigated, revealing differential sensitivity of plant-specific pathways to impaired nuclear transport. These findings attracted attention towards plant-specific cargoes that are transported over the nuclear envelope, unravelling connections between nuclear transport and components of signalling and developmental pathways. The current state of research in plants is summarised in comparison to yeast and vertebrate systems, and special emphasis is given to plant nuclear transport mutants

Molekulardynamik-Simulationen beliebig geformter Teilchen in zwei Dimensionen

In dieser Arbeit haben wir ein Simulationsprogramm vorgestellt, mit dem es möglich ist, die Bahnkurven und Rotationen von Partikeln zu berechnen, die die Gestalt von konvexen Polygonen haben. Wir berücksichtigten dabei eine elastische Wechselwirkungskraft, sowie Dissipation und Gleitreibung. Der wesentliche Vorteil dieses Modells gegenüber Molekulardynamik-Simulationen mit sphärischen Teilchen ist die Berücksichtigung von sterischen Effekten, die auf die geometrische Form der Teilchen zurückzuführen ist. Ein markantes Beispiel ist in der rotierenden Trommel der Winkel, den die Oberfläche des Granulates mit der Horizontalen bildet. Mit unserem Modell erhalten wir einen Wert, der im Bereich der experimentellen Befunde [137] liegt. Modelle, die sphärische Teilchen verwenden, liefern zu kleine Werte [129]. Zunächst präsentierten wir effiziente Algorithmen zum Erstellen von Voronoi-Zellen, die als Anfangskonfigurationen für Simulationen dicht gepackter Systeme sehr geeignet sind, da sie unregelmäßig geformte Polygone erzeugen, die die Ebene in isotroper Weise dicht parkettieren. Mit solchen Konfigurationen führten wir Scherzellenexperimente durch, bei denen die Schergeschwindigkeit und die Normalkraft variiert wurden. Wir fanden dabei Scherhärtung, d. h. ein Ansteigen der Scherkraft mit der Schergeschwindigkeit. Die Untersuchung der lokalen Rotation der Zellen führte uns zu der Beobachtung, daß sich zwei Regime inder Scherzelle ausbilden, das erste, in dem die Zellen rotieren und welches wir als Scherband bezeichnen, und das andere, in dem die Zellen weder rotieren noch sich relativ zueinander bewegen. Die Breite der Scherbänder ist sowohl von der Schergeschwindigkeit als auch von der Normalkraft abhängig. Es existiert ein Schwellwert für die Schergeschwindigkeit, oberhalb dessen die Scherbänder bis auf einen kleinen Restbereich in der Nähe der Wände die gesamte Scherzelle überspannen. An diesem Schwellwert ändert sich das Verhalten der Abhängigkeit der Scherkraft von der Schergeschwindigkeit. Unterhalb dieses Wertes steigt die Scherkraft wesentlich stärker mit der Schergeschwindigkeit an als über diesem Wert. Das gleiche Verhalten kann auch bei der Dilatanz, also bei der Ausdehnung des Systems, beobachtet werden. Die Begründung dieses Verhaltens sehen wir darin, daß die Verbreiterung der Scherzone aufgrund der sterischen Effekte durchdie Teilchengeometrie nur möglich ist, wenn das System dilatiert. Dilatation verursacht [...