Vitamin D: A modulator of cell proliferation and differentiation

Abstract 1,25-Dihydroxyvitamin D3, [1,25(OH)2D3], the biologically most active metabolite of vitamin D3, is involved in the regulation of calcium homeostasis and bone metabolism. Recently, receptors for 1,25(OH)2D3 have also been shown in cells and tissues not directly related to calcium homeostasis. Experimental data obtained with leukemic and cancer cell lines, both in vitro and in vivo, showed the effects of 1,25(OH)2D3 on cell differentiation and proliferation. However, high doses of the sterol have to be used to observe these effects. Additional studies are needed to establish whether 1,25(OH)2D3 or suitable analogues have a therapeutic potential in malignant diseases without unacceptable toxicity like the development of hypercalcemia

Future trends

A review with no ref

Improving the sensitivity of future GW observatories in the 1-10 Hz band: Newtonian and seismic noise

The next generation gravitational wave interferometric detectors will likely be underground detectors to extend the GW detection frequency band to frequencies below the Newtonian noise limit. Newtonian noise originates from the continuous motion of the Earth’s crust driven by human activity, tidal stresses and seismic motion, and from mass density fluctuations in the atmosphere. It is calculated that on Earth’s surface, on a typical day, it will exceed the expected GW signals at frequencies below 10 Hz. The noise will decrease underground by an unknown amount. It is important to investigate and to quantify this expected reduction and its effect on the sensitivity of future detectors, to plan for further improvement strategies. We report about some of these aspects. Analytical models can be used in the simplest scenarios to get a better qualitative and semi-quantitative understanding. As more complete modeling can be done numerically, we will discuss also some results obtained with a finite-element-based modeling tool. The method is verified by comparing its results with the results of analytic calculations for surface detectors. A key point about noise models is their initial parameters and conditions, which require detailed information about seismic motion in a real scenario. We will describe an effort to characterize the seismic activity at the Homestake mine which is currently in progress. This activity is specifically aimed to provide informations and to explore the site as a possible candidate for an underground observatory. Although the only compelling reason to put the interferometer underground is to reduce the Newtonian noise, we expect that the more stable underground environment will have a more general positive impact on the sensitivity.We will end this report with some considerations about seismic and suspension noise

Phosporylation of androgen receptor isoforms

Phosphorylation of the human AR (androgen receptor) is directly correlated with the appearance of at least three AR isoforms on an SDS/polyacrylamide gel. However, it is still not clear to what extent phosphorylation is involved in the occurrence of isoforms, which sites are phosphorylated and what are the functions of these phosphosites. The human AR was expressed in COS-1 cells and AR phosphorylation was studied further by mutational analyses and by using reversed-phase HPLC and MS. The reversed-phase HPLC elution pattern of the three isoforms revealed that Ser-650 was phosphorylated constitutively. After de novo synthesis, only Ser-650 was phosphorylated in the smallest isoform of 110 kDa and both Ser-650 and Ser-94 were phosphorylated in the second isoform of 112 kDa. The hormone-induced 114 kDa isoform shows an overall increase in phosphorylation of all the isolated peptides. The activities of the Ser-Ala substitution mutant S650A (Ser-650-->Ala) was found to be identical with wild-type AR activation in four different cell lines and three different functional analyses, e.g. transactivation, N- and C-terminal-domain interaction and co-activation by transcriptional intermediary factor 2. This was also found for mutants S94A and S515A with respect to transactivation. However, the S515A mutation, which should eliminate phosphorylation of the potential mitogen-activated protein kinase site, Ser-515, resulted in an unphosphorylated form of the peptide containing Ser-650. This suggests that Ser-515 can modulate phosphorylation at another site. The present study shows that the AR isoform pattern from AR de novo synthesis is directly linked to differential phosphorylation of a distinct set of sites. After mutagenesis of these sites, no major change in functional activity of the AR was observed

Maintenance of 2- and 3-connected components of graphs; Part I: 2- and 3-edge-connected components

In this paper a data structure is presented to efficiently maintain the 2and 3-edge-connected components of a graph, under insertions of edges in the graph. Starting from an "empty" graph of n nodes, the insertion of e edges takes O(n log n-[- e) time in total. The data structure allows for insertions of nodes also (in the same time bounds, taking n as the final number of nodes). Moreover

A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen family study

Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidat

Radio precursors to neutron star binary mergings

We discuss a possible generation of radio bursts preceding final stages of binary neutron star mergings which can be accompanied by short gamma-ray bursts. Detection of such bursts appear to be advantageous in the low-frequency radio band due to a time delay of ten to several hundred seconds required for radio signal to propagate in the ionized intergalactic medium. This delay makes it possible to use short gamma-ray burst alerts to promptly monitor specific regions on the sky by low-frequency radio facilities, especially by LOFAR. To estimate the strength of the radio signal, we assume a power-law dependence of the radio luminosity on the total energy release in a magnetically dominated outflow, as found in millisecond pulsars. Based on the planned LOFAR sensitivity at 120 MHz, we estimate that the LOFAR detection rate of such radio transients could be about several events per month from redshifts up to $z\sim1.3$ in the most optimistic scenario. The LOFAR ability to detect such events would crucially depend on exact efficiency of low-frequency radio emission mechanism.Comment: 6 pages, 2 figures, Accepted for publication in Astrophysics & Space Science. Largely extended version of ArXiv:0912.521

DOOM'd to Switch: Superior Cognitive Flexibility in Players of First Person Shooter Games

The interest in the influence of videogame experience on our daily life is constantly growing. “First Person Shooter” (FPS) games require players to develop a flexible mindset to rapidly react to fast moving visual and auditory stimuli, and to switch back and forth between different subtasks. This study investigated whether and to which degree experience with such videogames generalizes to other cognitive-control tasks. Video-game players (VGPs) and individuals with little to no videogame experience (NVGPs) performed on a task switching paradigm that provides a relatively well-established diagnostic measure of cognitive flexibility. As predicted, VGPs showed smaller switching costs (i.e., greater cognitive flexibility) than NVGPs. Our findings support the idea that playing FPS games promotes cognitive flexibility