Mouse cytoplasmic dynein intermediate chains: identification of new isoforms, alternative splicing and tissue distribution of transcripts

BACKGROUND: Intracellular transport of cargoes including organelles, vesicles, signalling molecules, protein complexes, and RNAs, is essential for normal function of eukaryotic cells. The cytoplasmic dynein complex is an important motor that moves cargos along microtubule tracks within the cell. In mammals this multiprotein complex includes dynein intermediate chains 1 and 2 which are encoded by two genes, Dync1i1 and Dync1i2. These proteins are involved in dynein cargo binding and dynein complexes with different intermediate chains bind to specific cargoes, although the mechanisms to achieve this are not known. The DYNC1I1 and DYNC1I2 proteins are translated from different splice isoforms, and specific forms of each protein are essential for the function of different dynein complexes in neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here we have undertaken a systematic survey of the dynein intermediate chain splice isoforms in mouse, basing our study on mRNA expression patterns in a range of tissues, and on bioinformatics analysis of mouse, rat and human genomic and cDNA sequences. We found a complex pattern of alternative splicing of both dynein intermediate chain genes, with maximum complexity in the embryonic and adult nervous system. We have found novel transcripts, including some with orthologues in human and rat, and a new promoter and alternative non-coding exon 1 for Dync1i2. CONCLUSIONS/SIGNIFICANCE: These data, including the cloned isoforms will be essential for understanding the role of intermediate chains in the cytoplasmic dynein complex, particularly their role in cargo binding within individual tissues including different brain regions

Efecto hepatoprotector del insaponificable de los aceites de oliva, linaza y sésamo contra la lesión hepática inducida por tetracloruro de carbono en ratas

In the present study, the hepatoprotective activity of the unsaponifiable matter (UNSAP) of olive oil, linseed, and sesame oils against CCl4-induced liver toxicity in rats was investigated. In a preliminary antioxidant study, UNSAP showed pronounced DPPH radical scavenging activity (IC50 6.2-10.8 mg/mL). The constituents of UNSAP were determined by GC-MS. The subcutaneous administration of CCl4, caused liver injury. The hepatoprotective effect of UNSAP was comparable to that of α-tocopherol, a standard antioxidant agent. The co-administration of the investigated UNSAP normalized the activities of serum marker enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Furthermore, the serum alkaline phosphatase (ALP) activity and hepatic malondialdehyde (MDA) level were found to be alleviated by pre-treatment with the UNSAP. A histopathological evaluation showed marked improvement in the liver of UNSAP- and α-Tocopherol-treated animals. The hepatoprotective effect could be attributed to the antioxidant characteristics of UNSAP.En el presente estudio, se investigó la actividad hepatoprotectora de la materia insaponificable (UNSAP) de los aceites de oliva, linaza y sésamo contra la toxicidad hepática inducida por CCl4 en ratas. En un estudio preliminar de antioxidantes, UNSAP mostró una pronunciada actividad de captación de radicales DPPH (IC50 6.2-10.8 mg / mL). Los constituyentes del UNSAP fueron determinados por GC-MS. La administración de CCl4, por vía subcutánea, causó lesión hepática. El efecto hepatoprotector del UNSAP fue comparable al del α-Tocoferol, un agente antioxidante estándar. La administración conjunta del UNSAP normalizó las actividades de las enzimas marcadoras séricas, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). Además, se encontró que la actividad de la fosfatasa alcalina en suero (ALP) y el nivel de malondialdehído hepático (MDA) se mitigan con el tratamiento previo con UNSAP. La evaluación histopatológica mostró una mejoría notable en el hígado de los animales tratados con UNSAP y α-Tocopherol. El efecto hepatoprotector podría atribuirse a las características antioxidantes de UNSAP

X-Ray Observations of the supernova remnant G21.5-0.9

We present the analysis of archival X-ray observations of the supernova remnant (SNR) G21.5-0.9. Based on its morphology and spectral properties, G21.5-0.9 has been classified as a Crab-like SNR. In their early analysis of the CHANDRA calibration data, Slane et al. (2000) discovered a low-surface-brightness, extended emission. They interpreted this component as the blast wave formed in the supernova (SN) explosion. In this paper, we present the CHANDRA analysis using a total exposure of ~150 ksec. We also include ROSAT and ASCA observations. Our analysis indicates that the extended emission is non-thermal -- a result in agreement with XMM observations. The entire remnant of radius ~ 2'.5 is best fitted with a power law model with a photon index steepening away from the center. The total unabsorbed flux in the 0.5-10 keV is 1.1E-10 erg/cm2/s with an 85% contribution from the 40" radius inner core. Timing analysis of the High-Resolution Camera (HRC) data failed to detect any pulsations. We put a 16% upper limit on the pulsed fraction. We derive the physical parameters of the putative pulsar and compare them with those of other plerions (such as the Crab and 3C 58). G21.5-0.9 remains the only plerion whose size in X-rays is bigger than in the radio. Deep radio observations will address this puzzle.Comment: 23 pages including 11 figures and 3 tables; accepted by ApJ June 22, 2001; to appear in Oct 20, 2001 issue of Ap

A Low Frequency Survey of the Galactic Plane Near l=11 degrees: Discovery of Three New Supernova Remnants

We have imaged a 1 deg^2 field centered on the known Galactic supernova remnant (SNR) G11.2-0.3 at 74, 330, and 1465 MHz with the Very Large Array radio telescope (VLA) and 235 MHz with the Giant Metrewave Radio Telescope (GMRT). The 235, 330, and 1465 MHz data have a resolution of 25 arcsec, while the 74 MHz data have a resolution of 100 arcsec. The addition of this low frequency data has allowed us to confirm the previously reported low frequency turnover in the radio continuum spectra of the two known SNRs in the field: G11.2-0.3 and G11.4-0.1 with unprecedented precision. Such low frequency turnovers are believed to arise from free-free absorption in ionized thermal gas along the lines of site to the SNRs. Our data suggest that the 74 MHz optical depths of the absorbing gas is 0.56 and 1.1 for G11.2-0.3 and G11.4-0.1, respectively. In addition to adding much needed low frequency integrated flux measurements for two known SNRs, we have also detected three new SNRs: G11.15-0.71, G11.03-0.05, and G11.18+0.11. These new SNRs have integrated spectral indices between -0.44 and -0.80. Because of confusion with thermal sources, the high resolution (compared to previous Galactic radio frequency surveys) and surface brightness sensitivity of our observations have been essential to the identification of these new SNRs. With this study we have more than doubled the number of SNRs within just a 1 deg^2 field of view in the inner Galactic plane. This result suggests that future low frequency observations of the Galactic plane of similar quality may go a long way toward alleviating the long recognized incompleteness of Galactic SNR catalogs.Comment: 31 pages, 9 figures. Figure 7 is in color. Accepted to A

Actividades antioxidantes, antiinflamatorias y citotóxicas de la fracción insaponificable de aceite de oliva virgen extra

The health benefits of olive oil are well-known. In this study, the unsaponifiable fraction of extra virgin olive oil (Unsap) was investigated for reducing power capacity, ferric reducing antioxidant power, fer-rous chelating activity and nitric oxide inhibition. The present study was also designed to evaluate the in vitro cytotoxic effect of the Unsap against human carcinoma cells. The anti-inflammatory potential of Unsap has been determined via the inhibition of Human Cyclooxygenases. The results showed that Unsap is efficient for ferric reducing antioxidant power and nitric oxide inhibition. Unsap has a selective effect as anti-inflammatory agent. The results showed moderate to good in vitro antitumor activities of Unsap against human liver, lung and pancreas cancer cells with IC50 ranging from 19.6 to 30.4 μg/mL and good selectivity index (≥ 2). In conclusion, Unsap represents a promising and safe antitumor and antioxidant material that supports the need for further investigation.Los beneficios para la salud del aceite de oliva son bien conocidos. En este estudio, se investigó la fracción insaponificable del aceite de oliva virgen extra (Insap) para reducir el poder antioxidante férrico, la actividad quelante ferrosa y la inhibición del óxido nítrico. El presente estudio también fue diseñado para evaluar el efecto citotóxico in vitro del Insap contra las células de carcinoma humano. La potencialidad antiinflamatoria del Insap se ha determinado mediante la inhibición de las ciclooxigenasas humanas. Los resultados mostraron que el Insap es eficiente para reducir el poder antioxidante férrico y la inhibición del óxido nítrico. El Insap tiene un efecto selectivo como agente antiinflamatorio. Los resultados mostraron actividades antitumorales in vitro del Insap de moderadas a buenas contra células de cáncer de hígado, pulmón y páncreas humano con una CI50 que varía de 19,6 a 30,4 μg/ml y por su buen índice de selectividad ( ≥ 2). En conclusión, el Insap contiene material antitumoral y antioxidante prometedor y seguro que será respaldado por investiga-ciones adicionales

DA495 - an aging pulsar wind nebula

We present a radio continuum study of the pulsar wind nebula (PWN) DA 495 (G65.7+1.2), including images of total intensity and linear polarization from 408 to 10550 MHz based on the Canadian Galactic Plane Survey and observations with the Effelsberg 100-m Radio Telescope. Removal of flux density contributions from a superimposed \ion{H}{2} region and from compact extragalactic sources reveals a break in the spectrum of DA 495 at 1.3 GHz, with a spectral index ${\alpha}={-0.45 \pm 0.20}$ below the break and ${\alpha}={-0.87 \pm 0.10}$ above it (${S}_\nu \propto{\nu^{\alpha}}$). The spectral break is more than three times lower in frequency than the lowest break detected in any other PWN. The break in the spectrum is likely the result of synchrotron cooling, and DA 495, at an age of $\sim$20,000 yr, may have evolved from an object similar to the Vela X nebula, with a similarly energetic pulsar. We find a magnetic field of $\sim$1.3 mG inside the nebula. After correcting for the resulting high internal rotation measure, the magnetic field structure is quite simple, resembling the inner part of a dipole field projected onto the plane of the sky, although a toroidal component is likely also present. The dipole field axis, which should be parallel to the spin axis of the putative pulsar, lies at an angle of {\sim}50\degr east of the North Celestial Pole and is pointing away from us towards the south-west. The upper limit for the radio surface brightness of any shell-type supernova remnant emission around DA 495 is $\Sigma_{1 GHz} \sim 5.4 \times 10^{-23}$ OAWatt m$^{-2}$ Hz$^{-1}$ sr$^{-1}$ (assuming a radio spectral index of $\alpha = -0.5$), lower than the faintest shell-type remnant known to date.Comment: 25 pages, accepted by Ap

Chandra Observations of the Crab-like Supernova Remnant G21.5-0.9

Chandra observations of the Crab-like supernova remnant G21.5-0.9 reveal a compact central core and spectral variations indicative of synchrotron burn-off of higher energy electrons in the inner nebula. The central core is slightly extended, perhaps indicating the presence of an inner wind-shock nebula surrounding the pulsar. No pulsations are observed from the central region, yielding an upper limit of ~40% for the pulsed fraction. A faint outer shell may be the first evidence of the expanding ejecta and blast wave formed in the initial explosion, indicating a composite nature for G21.5-0.9.Comment: 4 pages, 2 figures, formatted with emulateapj, submitted to ApJ

The Mediating Role of Bullying and Victimisation on the Relationship Between Problematic Internet Use and Substance Abuse Among Adolescents in the UK: The Parent–Child Relationship as a Moderator

Over the last decade, research into the negative effects of problematic internet use has greatly increased. The current study adopted a mediation-moderation model in exploring the relationship between problematic internet use and substance abuse (drinking, drug use, and smoking tobacco cigarettes) among 1,613 adolescents (aged 10–16) in the UK. The findings of the study revealed a significant positive correlation between problematic internet use and substance abuse, which is mediated by traditional and cyber bullying and victimisation. Furthermore, the parent–child relationship was found to be a protective factor that moderated the correlation between problematic internet use and substance abuse and the correlation between problematic internet use and traditional bullying. The study emphasises the critical need to reduce problematic internet use among adolescents as a risk factor for involvement in bullying as perpetrators and victims, in addition to substance abuse. Furthermore, the findings of the study highlight the importance of a good parent–child relationship as a protective factor among adolescents. In light of the findings of the study, interventions for reducing problematic internet use taking into account bullying and the parent–child relationship are needed among adolescents

Interpretation of localized surface nano-structures

Recent experiment was done to create surface nano-structures by extrusion of slow highly charged ions with LiNbO_3 single crystal. In this paper, we suggest a mechanism based on plasma expansion approach to explain the formation of the surface nano-structures. Furthermore, the effects of the physical parameters of the non-Maxwellian plasma on the created structures are examined