Alpha lipoic acid selectively inhibits proliferation and adhesion to fibronectin of v-H-ras-transformed 3Y1 cells

Here, we focused on the effects of racemic α-lipoic acid on proliferation and adhesion properties of 3Y1 rat fibroblasts and the v-H-ras-transformed derivative, HR-3Y1-2 cells. Racemic α-lipoic acid inhibited proliferation of HR-3Y1-2 but not 3Y1 cells at 0.3 and 1.0 mM. R-(+)-α-lipoic acid also inhibited proliferation of HR-3Y1-2 cells equivalent to that of racemic α-lipoic acid. In addition, racemic α-lipoic acid decreased intracellular reactive oxygen species levels in HR-3Y1 cells but not 3Y1 cells. Next, we evaluated the effects of racemic α-lipoic acid on cell adhesion to fibronectin. The results indicated that racemic α-lipoic acid decreased adhesive ability of HR-3Y1-2 cells to fibronectin-coated plates. As blocking antibody experiment revealed that β1-integrin plays a key role in cell adhesion in this experimental system, the effects of racemic α-lipoic acid on the expression of β1-integrin were examined. The results indicated that racemic α-lipoic acid selectively downregulated the expression of cell surface β1-integrin expression in HR-3Y1-2 cells. Intriguingly, exogenous hydrogen peroxide upregulated cell surface β1-integrin expression in 3Y1 cells. Taken together, these data suggest that reduction of intracellular reactive oxygen species levels by α-lipoic acid could be an effective means of ameliorating abnormal growth and adhesive properties in v-H-ras transformed cells

Detection of highly ionized O and Ne absorption lines in the X-ray spectrum of 4U1820-303 in the globular cluster, NGC 6624

We searched for absorption lines of highly ionized O and Ne in the energy spectra of two Low-mass X-ray binaries, 4U1820-303 in the globular cluster NGC6624 and Cyg X-2, observed with the Chandra LETG, and detected O VII, O VIII and Ne IX absorption lines for 4U1820-303. The equivalent width of the O VII K alpha line was 1.19 +0.47/-0.30 eV (90 % errors) and the significance was 6.5 sigma. Absorption lines were not detected for Cyg X-2 with a 90 % upper limit on the equivalent width of 1.06 eV for O VII K alpha. The absorption lines observed in 4U1820-303 are likely due to hot interstellar medium, because O will be fully photo-ionized if the absorbing column is located close to the binary system. The velocity dispersion is restricted to b = 200 - 420 km/s from consistency between O VII K alpha and K beta lines, Ne/O abundance ratio, and H column density. The average temperature and the O VII density are respectively estimated to be log(T[K]) = 6.2 - 6.3 and n(OVII) = (0.7 - 2.3) x 10^{-6} cm^{-3}. The difference of O VII column densities for the two sources may be connected to the enhancement of the soft X-ray background (SXB) towards the Galactic bulge region. Using the polytrope model of hot gas to account for the SXB we corrected for the density gradient and estimated the midplane O VII density at the solar neighborhood. The scale height of hot gas is then estimated using the AGN absorption lines. It is suggested that a significant portion of both the AGN absorption lines and the high-latitude SXB emission lines can be explained by the hot gas in our Galaxy.Comment: Accepted for publication in ApJ. 7 pages, 9 eps figure

Th e Dynamics of Capabilities in the Transition to Telecommunications Next Generation Networks

This paper examines the dynamics of capabilities in the transition to the socalled Next Generation Network (NGN), in the telecommunications industry. This transition is occurring in major incumbent fixed  telecommunications operators like BT (British Telecom), France Telecom and Deutsche Telekom, among others, where the innovation gap seems to be more challenging compared to mobile operators and cable TV companies. We analyze the capabilities development of BT in the United Kingdom, using documentary and interview data. The main conclusion is that, during the transition, capabilities vary rapidly in intensity: at the very beginning, strategic capabilities infl uence the decision-making and defi ne the transition, and then project capabilities are put in place to deploy the strategy, until functional capabilities take over and maintain the evolutionary path of the technology until a next major transition may occur

Abnormal social behavior, hyperactivity, impaired remote spatial memory, and increased D1-mediated dopaminergic signaling in neuronal nitric oxide synthase knockout mice

<p>Abstract</p> <p>Background</p> <p>Neuronal nitric oxide synthase (nNOS) is involved in the regulation of a diverse population of intracellular messenger systems in the brain. In humans, abnormal NOS/nitric oxide metabolism is suggested to contribute to the pathogenesis and pathophysiology of some neuropsychiatric disorders, such as schizophrenia and bipolar disorder. Mice with targeted disruption of the nNOS gene exhibit abnormal behaviors. Here, we subjected nNOS knockout (KO) mice to a battery of behavioral tests to further investigate the role of nNOS in neuropsychiatric functions. We also examined the role of nNOS in dopamine/DARPP-32 signaling in striatal slices from nNOS KO mice and the effects of the administration of a dopamine D1 receptor agonist on behavior in nNOS KO mice.</p> <p>Results</p> <p>nNOS KO mice showed hyperlocomotor activity in a novel environment, increased social interaction in their home cage, decreased depression-related behavior, and impaired spatial memory retention. In striatal slices from nNOS KO mice, the effects of a dopamine D1 receptor agonist, SKF81297, on the phosphorylation of DARPP-32 and AMPA receptor subunit GluR1 at protein kinase A sites were enhanced. Consistent with the biochemical results, intraperitoneal injection of a low dose of SKF81297 significantly decreased prepulse inhibition in nNOS KO mice, but not in wild-type mice.</p> <p>Conclusion</p> <p>These findings indicate that nNOS KO upregulates dopamine D1 receptor signaling, and induces abnormal social behavior, hyperactivity and impaired remote spatial memory. nNOS KO mice may serve as a unique animal model of psychiatric disorders.</p

An Arabidopsis SBP-domain fragment with a disrupted C-terminal zinc-binding site retains its tertiary structure

AbstractSQUAMOSA promoter-binding proteins (SBPs) form a major family of plant-specific transcription factors, mainly related to flower development. SBPs share a highly conserved DNA-binding domain of ∼80 amino acids (SBP domain), which contains two non-interleaved zinc-binding sites formed by eight conserved Cys or His residues. In the present study, an Arabidopsis SPL12 SBP-domain fragment that lacks a Cys residue involved in the C-terminal zinc-binding pocket was found to retain a folded structure, even though only a single Zn2+ ion binds to the fragment. Solution structure of this fragment determined by NMR is very similar to the previously determined structures of the full SBP domains of Arabidopsis SPL4 and SPL7. Considering the previous observations that chelating all the Zn2+ ions of SBPs resulted in the complete unfolding of the structure and that a mutation of the Cys residue equivalent to that described above impaired the DNA-binding activity, we propose that the Zn2+ ion at the N-terminal site is necessary to maintain the overall tertiary structure, while the Zn2+ ion at the C-terminal site is necessary for the DNA binding, mainly by guiding the basic C-terminal loop to correctly fit into the DNA groove

Behavioral Profiles of Three C57BL/6 Substrains

C57BL/6 inbred strains of mice are widely used in knockout and transgenic research. To evaluate the loss-of-function and gain-of-function effects of the gene of interest, animal behaviors are often examined. However, an issue of C57BL/6 substrains that is not always appreciated is that behaviors are known to be strongly influenced by genetic background. To investigate the behavioral characteristics of C57BL/6 substrains, we subjected C57BL/6J, C57BL/6N, and C57BL/6C mice to a behavior test battery. We performed both a regular scale analysis, in which experimental conditions were tightly controlled, and large-scale analysis from large number of behavioral data that we have collected so far through the comprehensive behavioral test battery applied to 700–2,200 mice in total. Significant differences among the substrains were found in the results of various behavioral tests, including the open field, rotarod, elevated plus maze, prepulse inhibition, Porsolt forced swim, and spatial working memory version of the eight-arm radial maze. Our results show a divergence of behavioral performance in C57BL/6 substrains, which suggest that small genetic differences may have a great influence on behavioral phenotypes. Thus, the genetic background of different substrains should be carefully chosen, equated, and considered in the interpretation of mutant behavioral phenotypes