Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF- II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A- immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs

Sensible heat transfer in the Gemini and Apollo pressure suits

Sensible heat transfer effects in Gemini and Apollo pressure suit

Comparison of Fermi-LAT and CTA in the region between 10-100 GeV

The past decade has seen a dramatic improvement in the quality of data available at both high (HE: 100 MeV to 100 GeV) and very high (VHE: 100 GeV to 100 TeV) gamma-ray energies. With three years of data from the Fermi Large Area Telescope (LAT) and deep pointed observations with arrays of Cherenkov telescope, continuous spectral coverage from 100 MeV to $\sim10$ TeV exists for the first time for the brightest gamma-ray sources. The Fermi-LAT is likely to continue for several years, resulting in significant improvements in high energy sensitivity. On the same timescale, the Cherenkov Telescope Array (CTA) will be constructed providing unprecedented VHE capabilities. The optimisation of CTA must take into account competition and complementarity with Fermi, in particularly in the overlapping energy range 10$-$100 GeV. Here we compare the performance of Fermi-LAT and the current baseline CTA design for steady and transient, point-like and extended sources.Comment: Accepted for Publication in Astroparticle Physic

Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein

p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control

DETERMINATION OF THE PARTIAL PRESSURE OF HALOTHANE (OR ISOFLURANE) IN BLOOD

A gas chromatographic method is described for the direct quantitative determination of the partial pressure of halothane {or isoflurane) in blood as well as the blood-gas partition coefficient. A head space technique and a flame ionization detector were used. Standard blood was obtained by equilibrating patients' blood with known gas concentrations in a tonometer. Using an infra-red analyser to measure the halothane gas concentration in the tonometer and within the anaesthetic system allowed for the direct comparison of the partial pressure in blood to the partial pressure in the inspired gas. Technical problems associated with this procedure, and with comparable methods, are discusse

Fermi-LAT and Suzaku Observations of the Radio Galaxy Centaurus B

Centaurus B is a nearby radio galaxy positioned in the Southern hemisphere close to the Galactic plane. Here we present a detailed analysis of about 43 months of accumulated Fermi-LAT data of the gamma-ray counterpart of the source initially reported in the 2nd Fermi-LAT catalog, and of newly acquired Suzaku X-ray data. We confirm its detection at GeV photon energies, and analyze the extension and variability of the gamma-ray source in the LAT dataset, in which it appears as a steady gamma-ray emitter. The X-ray core of Centaurus B is detected as a bright source of a continuum radiation. We do not detect however any diffuse X-ray emission from the known radio lobes, with the provided upper limit only marginally consistent with the previously claimed ASCA flux. Two scenarios that connect the X-ray and gamma-ray properties are considered. In the first one, we assume that the diffuse non-thermal X-ray emission component is not significantly below the derived Suzaku upper limit. In this case, modeling the inverse-Compton emission shows that the observed gamma-ray flux of the source may in principle be produced within the lobes. This association would imply that efficient in-situ acceleration of the radiating electrons is occurring and that the lobes are dominated by the pressure from the relativistic particles. In the second scenario, with the diffuse X-ray emission well below the Suzaku upper limits, the lobes in the system are instead dominated by the magnetic pressure. In this case, the observed gamma-ray flux is not likely to be produced within the lobes, but instead within the nuclear parts of the jet. By means of synchrotron self-Compton modeling we show that this possibility could be consistent with the broad-band data collected for the unresolved core of Centaurus B, including the newly derived Suzaku spectrum.Comment: Accepted for publication in A&A. 11 page