Search and analysis of giant radio galaxies with associated nuclei (SAGAN) -- I : New sample and multi-wavelength studies

We present the first results of a project called SAGAN, which is dedicated solely to the studies of relatively rare megaparsec-scale radio galaxies in the Universe, called giant radio galaxies (GRGs). We have identified 162 new GRGs primarily from the NVSS with sizes ranging from ~0.71 Mpc to 2.82 Mpc in the redshift range of ~0.03 - 0.95, of which 23 are hosted by quasars (giant radio quasars, GRQs). As part of the project SAGAN, we have created a database of all known GRGs, the GRG catalogue, from the literature (including our new sample); it includes 820 sources. For the first time, we present the multi-wavelength properties of the largest sample of GRGs. Our results establish that the distributions of the radio spectral index and the black hole mass of GRGs do not differ from the corresponding distributions of normal-sized radio galaxies (RGs). However, GRGs have a lower Eddington ratio (ER) than RGs. Using the mid-infrared data, we classified GRGs in terms of their accretion mode: either a high-power radiatively efficient high-excitation state, or a radiatively inefficient low-excitation state. We find that GRGs in high-excitation state statistically have larger sizes, stronger radio power, jet kinetic power, and higher ER than those in low-excitation state. Our analysis reveals a strong correlation between the ER and the scaled jet kinetic power, which suggests a disc-jet coupling. Our environmental study reveals that ~10% of all GRGs may reside at the centres of galaxy clusters, in a denser galactic environment, while the majority appears to reside in a sparse environment. We find that the probability of BCG as a GRG is quite low. We present new results for GRGs that range from black hole mass to large-scale environment properties. We discuss their formation and growth scenarios, highlighting the key physical factors that cause them to reach their gigantic size. Abridged.Comment: Accepted for publication in Astronomy & Astrophysics. 14 figures, 7 tables and 7 montages. Comments are welcome. "SAGAN Project website https://sites.google.com/site/anantasakyatta/sagan

Chop (Ddit3) Is Essential for D469del-COMP Retention and Cell Death in Chondrocytes in an Inducible Transgenic Mouse Model of Pseudoachondroplasia

Cartilage oligomeric matrix protein (COMP), a secreted glycoprotein synthesized by chondrocytes, regulates proliferation and type II collagen assembly. Mutations in the COMP gene cause pseudoachondroplasia and multiple epiphyseal dysplasia. Previously, we have shown that expression of D469del-COMP in transgenic mice causes intracellular retention of D469del-COMP, thereby recapitulating pseudoachondroplasia chondrocyte pathology. This inducible transgenic D469del-COMP mouse is the only in vivo model to replicate the critical cellular and clinical features of pseudoachondroplasia. Here, we report developmental studies of D469del-COMP-induced chondrocyte pathology from the prenatal period to adolescence. D469del-COMP retention was limited prenatally and did not negatively affect the growth plate until 3 weeks after birth. Results of immunostaining, transcriptome analysis, and qRT-PCR suggest a molecular model in which D469del-COMP triggers apoptosis during the first postnatal week. By 3 weeks (when most chondrocytes are retaining D469del-COMP), inflammation, oxidative stress, and DNA damage contribute to chondrocyte cell death by necroptosis. Importantly, by crossing the D469del-COMP mouse onto a Chop null background (Ddit3 null), thereby eliminating Chop, the unfolded protein response was disrupted, thus alleviating both D469del-COMP intracellular retention and premature chondrocyte cell death. Chop therefore plays a significant role in processes that mediate D469del-COMP retention. Taken together, these results suggest that there may be an optimal window before the induction of significant D469del-COMP retention during which endoplasmic reticulum stress could be targeted

The Effects of Protamine on a Murine Leukemia Virus

This study indicated that: (1) i.p. inoculation of protamine into (Rauscher) leukemic mice increased their X death time, (2) protamine was more toxic for leukemic than normal mice and (3) the in vitro reaction between Rauscher virus and protamine reduced its infectivity for mice

Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes.

AIMS/HYPOTHESIS: The glucose transporter GLUT4 is present mainly in insulin-responsive tissues of fat, heart and skeletal muscle and is translocated from intracellular membrane compartments to the plasma membrane (PM) upon insulin stimulation. The transit of GLUT4 to the PM is known to be dependent on a series of Rab proteins. However, the extent to which the activity of these Rabs is regulated by the action of insulin action is still unknown. We sought to identify insulin-activated Rab proteins and Rab effectors that facilitate GLUT4 translocation. METHODS: We developed a new photoaffinity reagent (Bio-ATB-GTP) that allows GTP-binding proteomes to be explored. Using this approach we screened for insulin-responsive GTP loading of Rabs in primary rat adipocytes. RESULTS: We identified Rab3B as a new candidate insulin-stimulated G-protein in adipocytes. Using constitutively active and dominant negative mutants and Rab3 knockdown we provide evidence that Rab3 isoforms are key regulators of GLUT4 translocation in adipocytes. Insulin-stimulated Rab3 GTP binding is associated with disruption of the interaction between Rab3 and its negative effector Noc2. Disruption of the Rab3-Noc2 complex leads to displacement of Noc2 from the PM. This relieves the inhibitory effect of Noc2, facilitating GLUT4 translocation. CONCLUSIONS/INTERPRETATION: The discovery of the involvement of Rab3 and Noc2 in an insulin-regulated step in GLUT4 translocation suggests that the control of this translocation process is unexpectedly similar to regulated secretion and particularly pancreatic insulin-vesicle release

The molecular polar disc in NGC 2768

We present CO(1-0) and CO(2-1) maps of the molecular polar disc in the elliptical galaxy NGC 2768 obtained at the IRAM Plateau de Bure Interferometer. The maps have a resolution of 2.6" x 2.3" and 1.2" x 1.2" for the CO(1-0) and CO(2-1) lines, respectively. The CO maps complete the unique picture of the interstellar medium (ISM) of NGC 2768; the dust, molecular gas, ionised gas and neutral hydrogen (HI) trace the recent acquisition of cold and cool gas over two orders of magnitude in radii (and much more in density). In agreement with the other ISM components, the CO distribution extends nearly perpendicularly to the photometric major axis of the galaxy. Velocity maps of the CO show a rotating polar disc or ring in the inner kiloparsec. This cool gas could lead to kinematic substructure formation within NGC 2768. However, the stellar velocity field and H-beta absorption linestrength maps from the optical integral-field spectrograph SAURON give no indication of a young and dynamically cold stellar population coincident with the molecular polar disc. Very recent or weak star formation, undetectable in linestrengths, nevertheless remains a possibility and could be at the origin of some of the ionised gas observed. Millimetre continuum emission was also detected in NGC 2768, now one of only a few low-luminosity active galactic nuclei with observed millimetre continuum emission.Comment: Accepted for publication in MNRAS, 11 pages, 8 figure

A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications

The components of many signaling pathways have been identified and there is now a need to conduct quantitative data-rich temporal experiments for systems biology and modeling approaches to better understand pathway dynamics and regulation. Here we present a modified Western blotting method that allows the rapid and reproducible quantification and analysis of hundreds of data points per day on proteins and their phosphorylation state at individual sites. The approach is of particular use where samples show a high degree of sample-to-sample variability such as primary cells from multiple donors. We present a case study on the analysis of >800 phosphorylation data points from three phosphorylation sites in three signaling proteins over multiple time points from platelets isolated from ten donors, demonstrating the technique's potential to determine kinetic and regulatory information from limited cell numbers and to investigate signaling variation within a population. We envisage the approach being of use in the analysis of many cellular processes such as signaling pathway dynamics to identify regulatory feedback loops and the investigation of potential drug/inhibitor responses, using primary cells and tissues, to generate information about how a cell's physiological state changes over time

Joint degeneration in a mouse model of pseudoachondroplasia: ER stress, inflammation, and block of autophagy

Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia associated with premature joint degeneration, is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur in articular chondrocytes of MT-COMP mice, a murine model of PSACH. The accumulation of mutant-COMP in the ER occurred early in MT-COMP articular chondrocytes and stimulated inflammation (TNFα) at 4 weeks, and articular chondrocyte death increased at 8 weeks while ER stress through CHOP was elevated by 12 weeks. Importantly, blockage of autophagy (pS6), the major mechanism that clears the ER, sustained cellular stress in MT-COMP articular chondrocytes. Degeneration of MT-COMP articular cartilage was similar to that observed in PSACH and was associated with increased MMPs, a family of degradative enzymes. Moreover, chronic cellular stresses stimulated senescence. Senescence-associated secretory phenotype (SASP) may play a role in generating and propagating a pro-degradative environment in the MT-COMP murine joint. The loss of CHOP or resveratrol treatment from birth preserved joint health in MT-COMP mice. Taken together, these results indicate that ER stress/CHOP signaling and autophagy blockage are central to mutant-COMP joint degeneration, and MT-COMP mice joint health can be preserved by decreasing articular chondrocyte stress. Future joint sparing therapeutics for PSACH may include resveratrol