Spatio-temporal images of growth-factor-induced activation of Ras and Rap1.

G proteins of the Ras family function as molecular switches in many signalling cascades; however, little is known about where they become activated in living cells. Here we use FRET (fluorescent resonance energy transfer)-based sensors to report on the spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Epidermal growth factor activated Ras at the peripheral plasma membrane and Rap1 at the intracellular perinuclear region of COS-1 cells. In PC12 cells, nerve growth factor-induced activation of Ras was initiated at the plasma membrane and transmitted to the whole cell body. After three hours, high Ras activity was observed at the extending neurites. By using the FRAP (fluorescence recovery after photobleaching) technique, we found that Ras at the neurites turned over rapidly; therefore, the sustained Ras activity at neurites was due to high GTP/GDP exchange rate and/or low GTPase activity, but not to the retention of the active Ras. These observations may resolve long-standing questions as to how Ras and Rap1 induce different cellular responses and how the signals for differentiation and survival are distinguished by neuronal cells.     

Left–right asymmetry in zebrafish

In vertebrates, internal organs are positioned asymmetrically across the left-right (LR) axis, placing them in a defined area within the body. This LR asymmetric placement is a conserved feature of the vertebrate body plan. Events determining LR asymmetry occur during embryonic development, and are regulated by the coordinated action of genetic mechanisms that are evolutionarily conserved among vertebrates. Recent studies using zebrafish have provided new insights into how the Kupffer's vesicle organizer region is generated, and how it relays LR asymmetry information to the lateral plate mesoderm. In this review, we summarize recent advances in zebrafish and describe our current understanding of the mechanisms underlying these processes.     

A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population

Through a genome-wide association analysis with a total of 7,035 individuals with duodenal ulcer and 25,323 controls from Japan, we identified two susceptibility loci at the PSCA gene (encoding prostate stem cell antigen) at 8q24 and at the ABO blood group locus at 9q34. The C allele of rs2294008 at PSCA was associated with increased risk of duodenal ulcer (odds ratio (OR) = 1.84; P = 3.92 × 10(-33)) in a recessive model but was associated with decreased risk of gastric cancer (OR = 0.79; P = 6.79 × 10(-12)), as reported previously. The T allele of rs2294008 encodes a translation initiation codon upstream of the reported site and changes protein localization from the cytoplasm to the cell surface. rs505922 at ABO was also associated with duodenal ulcer in a recessive model (OR = 1.32; P = 1.15 × 10(-10)). Our findings demonstrate a role for genetic variants in the pathogenesis of duodenal ulcer.     

A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15

F cells measure the presence of fetal hemoglobin, a heritable quantitative trait in adults that accounts for substantial phenotypic diversity of sickle cell disease and beta thalassemia. We applied a genome-wide association mapping strategy to individuals with contrasting extreme trait values and mapped a new F cell quantitative trait locus to BCL11A, which encodes a zinc-finger protein, on chromosome 2p15. The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance.     

Solution-processed silicon films and transistors

The use of solution processes-as opposed to conventional vacuum processes and vapour-phase deposition-for the fabrication of electronic devices has received considerable attention for a wide range of applications, with a view to reducing processing costs. In particular, the ability to print semiconductor devices using liquid-phase materials could prove essential for some envisaged applications, such as large-area flexible displays. Recent research in this area has largely been focused on organic semiconductors, some of which have mobilities comparable to that of amorphous silicon (a-Si); but issues of reliability remain. Solution processing of metal chalcogenide semiconductors to fabricate stable and high-performance transistors has also been reported. This class of materials is being explored as a possible substitute for silicon, given the complex and expensive manufacturing processes required to fabricate devices from the latter. However, if high-quality silicon films could be prepared by a solution process, this situation might change drastically. Here we demonstrate the solution processing of silicon thin-film transistors (TFTs) using a silane-based liquid precursor. Using this precursor, we have prepared polycrystalline silicon (poly-Si) films by both spin-coating and ink-jet printing, from which we fabricate TFTs with mobilities of 108 cm2 V(-1) s(-1) and 6.5 cm2 V(-1) s(-1), respectively. Although the processing conditions have yet to be optimized, these mobilities are already greater than those that have been achieved in solution-processed organic TFTs, and they exceed those of a-Si TFTs (< or = 1 cm2 V(-1) s(-1)).     

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.     

Observation of individual vortices trapped along columnar defects in high-temperature superconductors

Many superconductors do not entirely expel magnetic flux-rather, magnetic flux can penetrate the superconducting state in the form of vortices. Moving vortices create resistance, so they must be 'pinned' to permit dissipationless current flow. This is a particularly important issue for the high-transition-temperature superconductors, in which the vortices move very easily. Irradiation of superconducting samples by heavy ions produces columnar defects, which are considered to be the optimal pinning traps when the orientation of the column coincides with that of the vortex line. Although columnar defect pinning has been investigated using macroscopic techniques, it has hitherto been impossible to resolve individual vortices intersecting with individual defects. Here we achieve the resolution required to image vortex lines and columnar defects in Bi2Sr2CaCu2O8+delta (Bi-2212) thin films, using a 1-MV field-emission electron microscope. For our thin films, we find that the vortex lines at higher temperatures are trapped and oriented along tilted columnar defects, irrespective of the orientation of the applied magnetic field. At lower temperatures, however, vortex penetration always takes place perpendicular to the film plane, suggesting that intrinsic 'background' pinning in the material now dominates.     

Effect of bilirubin on glucose oxidation in red cells

Zusammenfassung Es wird nachgewiesen, dass die¹⁴CO₂-Herstellung aus¹⁴C-U-Glukose durch rote Blutkörperchen in Anwesenheit von Methylenblau sich um das etwa 20fache vermehrt. Der Einfluss von Methylenblau wurde auffallend herabgesetzt, wenn Bilirubin dem Erythrozytensystem mit Methylenblau zugesetzt wurde.     

Repeated injections of energy in the first 600 ms of the giant flare of SGR 1806-20

The massive flare of 27 December 2004 from the soft gamma-ray repeater SGR 1806-20, a possible magnetar, saturated almost all gamma-ray detectors, meaning that the profile of the pulse was poorly characterized. An accurate profile is essential to determine physically what was happening at the source. Here we report the unsaturated gamma-ray profile for the first 600 ms of the flare, with a time resolution of 5.48 ms. The peak of the profile (of the order of 10(7) photons cm(-2) s(-1)) was reached approximately 50 ms after the onset of the flare, and was then followed by a gradual decrease with superposed oscillatory modulations possibly representing repeated energy injections with approximately 60-ms intervals. The implied total energy is comparable to the stored magnetic energy in a magnetar (approximately 10(47) erg) based on the dipole magnetic field intensity (approximately 10(15) G), suggesting either that the energy release mechanism was extremely efficient or that the interior magnetic field is much stronger than the external dipole field.