Localization of tyrosine kinase-coding region in v-abl oncogene by the expression of v-abl-encoded proteins in bacteria

A series of plasmids containing different segments of the v-abl oncogene have been constructed to express different portions of the v- abl protein in bacteria. The tyrosine kinase activity of these proteins was determined by an in vitro assay employing histones or angiotensin II as substrates for the v-abl-encoded tyrosine kinase. These experiments show that the 5'-1.2 kilobases of v-abl is necessary and sufficient to produce an active tyrosine kinase which is functional as a monomeric soluble protein. The kinase-coding region corresponds to the minimal region of v-abl required for the transformation of fibroblasts. The kinase-coding region also coincides with the conserved protein sequences which are found in other tyrosine kinases. A compact domain of the v-abl protein including this kinase-coding region can accumulate to high levels in bacteria. The C-terminal region of the v- abl protein is not needed for the kinase activity and is rapidly degraded in bacteria

Undecidable properties of self-affine sets and multi-tape automata

We study the decidability of the topological properties of some objects coming from fractal geometry. We prove that having empty interior is undecidable for the sets defined by two-dimensional graph-directed iterated function systems. These results are obtained by studying a particular class of self-affine sets associated with multi-tape automata. We first establish the undecidability of some language-theoretical properties of such automata, which then translate into undecidability results about their associated self-affine sets.Comment: 10 pages, v2 includes some corrections to match the published versio

Mass and dust in the disk of a spiral lens galaxy

Gravitational lensing is a potentially important probe of spiral galaxy structure, but only a few cases of lensing by spiral galaxies are known. We present Hubble Space Telescope and Magellan observations of the two-image quasar PMN J2004-1349, revealing that the lens galaxy is a spiral galaxy. One of the quasar images passes through a spiral arm of the galaxy and suffers 3 magnitudes of V-band extinction. Using simple lens models, we show that the mass quadrupole is well-aligned with the observed galaxy disk. A more detailed model with components representing the bulge and disk gives a bulge-to-disk mass ratio of 0.16 +/- 0.05. The addition of a spherical dark halo, tailored to produce an overall flat rotation curve, does not change this conclusion.Comment: ApJ, in press [9pp, 7 figs

Black Hole and Neutron Star Transients in Quiescence

We consider the X-ray luminosity difference between neutron star and black hole soft X-ray transients (NS and BH SXTs) in quiescence. The current observational data suggest that BH SXTs are significantly fainter than NS SXTs. The luminosities of quiescent BH SXTs are consistent with the predictions of binary evolution models for the mass transfer rate if (1) accretion occurs via an ADAF in these systems and (2) the accreting compact objects have event horizons. The luminosities of quiescent NS SXTs are not consistent with the predictions of ADAF models when combined with binary evolution models, unless most of the mass accreted in the ADAF is prevented from reaching the neutron star surface. We consider the possibility that mass accretion is reduced in quiescent NS SXTs because of an efficient propeller and develop a model of the propeller effect that accounts for the observed luminosities. We argue that modest winds from ADAFs are consistent with the observations while strong winds are probably not.Comment: LateX, 37 pages, 7 figures; Accepted for publication in The Astrophysical Journa

Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids

SummaryObjectiveOur present study examined the effect of intra-articular cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression and the concomitant changes in excitatory amino acids' (EAAs) levels of the anterior cruciate ligament-transected (ACLT) knee joint dialysates.MethodsOA was induced in Wistar rats by anterior cruciate ligament transection of the knee of one hindlimb, the other was left unoperated and untreated. Rats were placed into four groups: Group ACLT/P received intra-articular parecoxib injection (100μg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks after surgery. Group ACLT/S received the same procedure as group ACLT/P with saline injection instead. Naïve (Naïve/P) rats received only intra-articular parecoxib injection in one knee once a week for 5 consecutive weeks without surgery. The sham-operated rats underwent arthrotomy only without treatment. Twenty weeks after surgery, knee joint dialysates were collected and EAAs' concentration was assayed by high-performance liquid chromatography, and gross morphology and histopathology (Mankin and synovitis grading) were examined on the medial femoral condyles and synovia.ResultsParecoxib alone had no effect on cartilage and synovium of normal knees in Naïve/P rats. In ACLT/P rats, parecoxib treatment showed a significant inhibition of cartilage degeneration of the medial femoral condyle at both the macroscopic level (1.15±0.17 vs 2.55±0.12, P<0.05) and the Mankin scores (3.03±0.28 vs 8.82±0.43, P<0.05). Intra-articular parecoxib injection also suppressed the synovial inflammation of ACLT joint compared to the ACLT/S group (3.92±0.41 vs 9.25±0.32, P<0.05). Moreover, glutamate and aspartate levels were also significantly reduced in the ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2±9.4% vs 189.5±17.0%, P<0.05 and 98.2±11.6% vs 175.3±12.4%, P<0.05, respectively).ConclusionThis study shows that intra-articular injection of COX-2 inhibitor parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a reduction of glutamate and aspartate concentration in the ACLT joint dialysates. From our present results, we suggested that intra-articular parecoxib injection, in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may also play a role in inhibiting the traumatic knee injury induced OA progression

The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/

Association of Ataxia Telangiectasia Mutated (ATM) Gene Mutation/Deletion with Rhabdomyosarcoma – retraction

<p>Abstract</p> <p>Background</p> <p>Rhabdomyosarcoma is a common malignancy in children. There are two major types of rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of rhabdomyosarcoma is frequently associated with chromosome translocation t(2, 13) and poor clinical prognosis. Pathogenesis of rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion.</p> <p>Result</p> <p>Totally 17 cases of rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control.</p> <p>Conclusion</p> <p>These results suggest a link of ATM gene deletion/mutation with rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DNA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of rhabdomyosarcoma.</p

Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model†

OBJECTIVES The pre-treatment of tumour neovessels by low-level photodynamic therapy (PDT) improves the distribution of concomitantly administered systemic chemotherapy. The mechanism by which PDT permeabilizes the tumour vessel wall is only partially known. We have recently shown that leukocyte-endothelial cell interaction is essential for photodynamic drug delivery to normal tissue. The present study investigates whether PDT enhances drug delivery in malignant mesothelioma and whether it involves comparable mechanisms of actions. METHODS Human mesothelioma xenografts (H-meso-1) were grown in the dorsal skinfold chambers of 28 nude mice. By intravital microscopy, the rolling and recruitment of leukocytes were assessed in tumour vessels following PDT (Visudyne® 400μg/kg, fluence rate 200mW/cm2and fluence 60J/cm2) using intravital microscopy. Likewise, the distribution of fluorescently labelled macromolecular dextran (FITC-dextran, MW 2000kDa) was determined after PDT. Study groups included no PDT, PDT, PDT plus a functionally blocking anti-pan-selectin antibody cocktail and PDT plus isotype control antibody. RESULTS PDT significantly enhanced the extravascular accumulation of FITC-dextran in mesothelioma xenografts, but not in normal tissue. PDT significantly increased leukocyte-endothelial cell interaction in tumour. While PDT-induced leukocyte recruitment was significantly blunted by the anti-pan-selectin antibodies in the tumour xenograft, this manipulation did not affect the PDT-induced extravasation of FITC-dextran. CONCLUSIONS Low-level PDT pre-treatment selectively enhances the uptake of systemically circulating macromolecular drugs in malignant mesothelioma, but not in normal tissue. Leukocyte-endothelial cell interaction is not required for PDT-induced drug delivery to malignant mesotheliom

Investigating electron interacting dark matter

Some extensions of the Standard Model provide Dark Matter candidate particles which can have a dominant coupling with the lepton sector of the ordinary matter. Thus, such Dark Matter candidate particles ($\chi^{0}$) can be directly detected only through their interaction with electrons in the detectors of a suitable experiment, while they are lost by experiments based on the rejection of the electromagnetic component of the experimental counting rate. These candidates can also offer a possible source of the 511 keV photons observed from the galactic bulge. In this paper this scenario is investigated. Some theoretical arguments are developed and related phenomenological aspects are discussed. Allowed intervals and regions for the characteristic phenomenological parameters of the considered model and of the possible mediator of the interaction are also derived considering the DAMA/NaI data.Comment: 16 pages, 6 figures. Accepted for publication in PRD. One typo correcte