Intracellular NAD(H) levels control motility and invasion of glioma cells

Oncogenic transformation involves reprogramming of cell metabolism, whereby steady-state levels of intracellular NAD⁺ and NADH can undergo dramatic changes while ATP concentration is generally well maintained. Altered expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD⁺-salvage, accompanies the changes in NAD(H) during tumorigenesis. Here, we show by genetic and pharmacological inhibition of NAMPT in glioma cells that fluctuation in intracellular [NAD(H)] differentially affects cell growth and morphodynamics, with motility/invasion capacity showing the highest sensitivity to [NAD(H)] decrease. Extracellular supplementation of NAD⁺ or re-expression of NAMPT abolished the effects. The effects of NAD(H) decrease on cell motility appeared parallel coupled with diminished pyruvate-lactate conversion by lactate dehydrogenase (LDH) and with changes in intracellular and extracellular pH. The addition of lactic acid rescued and knockdown of LDH-A replicated the effects of [NAD(H)] on motility. Combined, our observations demonstrate that [NAD(H)] is an important metabolic component of cancer cell motility. Nutrient or drug-mediated modulation of NAD(H) levels may therefore represent a new option for blocking the invasive behavior of tumors.     

Detection of a radio counterpart to the 27 December 2004 giant flare from SGR 1806-20

It was established over a decade ago that the remarkable high-energy transients known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called 'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading radio counterpart to this event. We began a monitoring programme from 0.2 to 250 GHz and obtained a high-resolution 21-cm radio spectrum that traces the intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields the first direct distance measurement of SGR 1806-20: the source is located at a distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If correct, our distance estimate lowers the total energy of the explosion and relaxes the demands on theoretical models. The energetics and the rapid decay of the radio source are not compatible with the afterglow model that is usually invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio emission arises from the debris ejected during the explosion.     

Effect of partition coefficient on microsegregation during solidification of aluminium alloys

In the modeling of microsegregation, the partition coefficient is usually calculated using data from the equilibrium phase diagrams. The aim of this study was to experimentally and theoretically analyze the partition coefficient in binary aluminum-copper alloys. The samples were analyzed by differential thermal analysis (DTA), which were melted and quenched from different temperatures during solidification. The mass fraction and composition of phases were measured by image processing and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectroscopy (EDS) unit. These data were used to calculate as the experimental partition coefficients with four different methods. The experimental and equilibrium partition coefficients were used to model the concentration profile in the primary phase. The modeling results show that the profiles calculated by the experimental partition coefficients are more consistent with the experimental profiles, compared to those calculated using the equilibrium partition coefficients.     

Cloning of a gene that is rearranged in patients with choroideraemia

Choroideraemia (tapetochoroidal dystrophy, TCD), a common form of X-linked blindness, is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. Previous studies have assigned the TCD gene to a small segment of the Xq21 band. By making use of reverse genetics strategies we have isolated eight overlapping complementary DNA clones from the same chromosomal region. The corresponding gene is expressed in retina, choroid and retinal pigment epithelium. The cDNAs encompass an open reading frame of 948 base pairs that is structurally altered in eight TCD patients with deletions, and in a female patient with a balanced translocation involving Xq21. These findings provide strong evidence that we have cloned the gene underlying choroideraemia. Elucidation of its function should provide new insights into the molecular mechanisms responsible for this disorder and other hereditary retinopathies.