Multiple mechanisms determine ER network morphology during the cell cycle in Xenopus egg extracts

In metazoans the endoplasmic reticulum (ER) changes during the cell cycle, with the nuclear envelope (NE) disassembling and reassembling during mitosis and the peripheral ER undergoing extensive remodeling. Here we address how ER morphology is generated during the cell cycle using crude and fractionated Xenopus laevis egg extracts. We show that in interphase the ER is concentrated at the microtubule (MT)-organizing center by dynein and is spread by outward extension of ER tubules through their association with plus ends of growing MTs. Fusion of membranes into an ER network is dependent on the guanosine triphosphatase atlastin (ATL). NE assembly requires fusion by both ATL and ER-soluble N-ethyl-maleimide–sensitive factor adaptor protein receptors. In mitotic extracts, the ER converts into a network of sheets connected by ER tubules and loses most of its interactions with MTs. Together, these results indicate that fusion of ER membranes by ATL and interaction of ER with growing MT ends and dynein cooperate to generate distinct ER morphologies during the cell cycle

Multiwavelength Monitoring of the Narrow-Line Seyfert 1 Galaxy Akn 564. I. ASCA Observations and the Variability of the X-ray Spectral Components

We present a 35 day ASCA observation of the NLS1 Akn 564, which was part of a multiwavelength AGN Watch monitoring campaign. Akn 564 shows a photon index varying across the range 2.45--2.72. The presence of the soft hump component below 1 keV, previously detected in ASCA data, is confirmed. Time-resolved spectroscopy with ~daily sampling reveals a distinction in the variability of the soft hump and power-law components over a timescale of weeks, with the hump varying by a factor of 6 across the 35-day observation compared to a factor 4 in the power-law. Flux variations in the power-law component are measured down to a timescale of ~1000s and accompanying spectral variability suggests the soft hump is not well-correlated with the power-law on such short timescales. We detect Fe Ka and a blend of Fe Kb plus Ni Ka, indicating an origin in highly ionized gas. Variability measurements constrain the bulk of the Fe Ka to originate within a light week of the nucleus. The large EW of the emission lines may be due to high metallicity in NLS1s, supporting some evolutionary models for AGN.Comment: 41 pages, 15 figures. Accepted for publication in the Astrophysical Journal (v3 has final fixes for publication

Modeling the UBVRI time delays in Mrk 335

We develop a model of time delays between the continuum bands in the Narrow Line Seyfert 1 galaxy Mrk 335 to explain the observed delays measured in this source. We consider two geometries: an accretion disk with fully ionized warm absorber of considerable optical depth, located close to the symmetry axis, and an accretion disk with a hot corona. Both media lead to significant disk irradiation but the disk/corona geometry gives lower values of the time delays. Only the disk/corona models give results consistent with measurements of Sergeev et al., and a low value of the disk inclination is favored. The presence of an optically thick, fully ionized outflow is ruled out at the 2-sigma level.Comment: MNRAS (in press

A 12-day ASCA Observation of the Narrow-Line Seyfert 1 Galaxy Ton S180: Time-Selected Spectroscopy

We present an analysis of the X-ray variability properties of the NLS1 galaxy Ton S180, based upon a 12-day continuous ASCA observation. We observe flux variations of a factor of 3.5 in the 0.7-1.3 keV band and 3.9 in the 2-10 keV band.Time-resolved spectroscopy (~1d sampling) reveals that the broad `soft hump' component at energies <2 keV shows flux variations on timescales down to 1 day that are well correlated with the photon index and the 2-10 keV band flux. A broad Fe K$\alpha$ emission is detected. There is a evidence for a narrow Fe K$\alpha$ line at ~6.8 keV, indicating an origin in ionized material. We do not detect significant variations of the line flux or EW on ~1 day-1 week timescales. The softness ratio reveals spectral variability on timescales down to ~1000 s, indicating that the power-law continuum and soft hump fluxes are not well correlated on this timescale. It also shows a slow decline across the observation, due to a combination of the different time-variability of the power-law continuum and soft hump flux on timescales of ~1 week. The X-ray emission originates within 12 Schwarzschild radii, and the amplitudes and timescales of the rapid variations we observed are consistent with those expected within disk-corona models. The soft hump variability timescale rules out an origin in large scale components (circumnuclear starburst). The $\Gamma$-soft hump correlation is consistent with the soft hump being produced by up-scattering of the accretion disk radiation within a flaring disk corona.Comment: 11 pages, 9 figures; accepted for publication in The Astrophysical Journal, LaTeX emulateapj.st

Observational tests of the galaxy formation process

The mutual feedback between star formation and nuclear activity in large spheroidal galaxies may be a key ingredient to overcome several difficulties plaguing current semi-analytic models for galaxy formation. We discuss some observational implications of the model by Granato et al. (2003) for the co-evolution of galaxies and active nuclei at their centers and stress the potential of the forthcoming surveys of the Sunyaev-Zeldovich effect on arcminute scales, down to $\mu$K levels, to investigate the early galaxy formation phases, difficult to access by other means.Comment: 6, pages, 1 figure, to appear in proc. of the meeting "Baryons on Cosmic Structures", Roma, October 20-21, 200

The SV40 Late Protein VP4 Is a Viroporin that Forms Pores to Disrupt Membranes for Viral Release

Nonenveloped viruses are generally released by the timely lysis of the host cell by a poorly understood process. For the nonenveloped virus SV40, virions assemble in the nucleus and then must be released from the host cell without being encapsulated by cellular membranes. This process appears to involve the well-controlled insertion of viral proteins into host cellular membranes rendering them permeable to large molecules. VP4 is a newly identified SV40 gene product that is expressed at late times during the viral life cycle that corresponds to the time of cell lysis. To investigate the role of this late expressed protein in viral release, water-soluble VP4 was expressed and purified as a GST fusion protein from bacteria. Purified VP4 was found to efficiently bind biological membranes and support their disruption. VP4 perforated membranes by directly interacting with the membrane bilayer as demonstrated by flotation assays and the release of fluorescent markers encapsulated into large unilamellar vesicles or liposomes. The central hydrophobic domain of VP4 was essential for membrane binding and disruption. VP4 displayed a preference for membranes comprised of lipids that replicated the composition of the plasma membranes over that of nuclear membranes. Phosphatidylethanolamine, a lipid found at high levels in bacterial membranes, was inhibitory against the membrane perforation activity of VP4. The disruption of membranes by VP4 involved the formation of pores of ∼3 nm inner diameter in mammalian cells including permissive SV40 host cells. Altogether, these results support a central role of VP4 acting as a viroporin in the perforation of cellular membranes to trigger SV40 viral release

Reply to Nielsen et al. social mindfulness is associated with countries’ environmental performance and individual environmental concern

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From local social mindfulness to global sustainability efforts?

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NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Cappelli et al. reported that Nitric Oxide Synthase 1 Adaptor Protein is a co-regulated transcript of the TAR DNA-binding protein 43 kDa, reduced in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients with TAR DNA-binding protein 43 kDa pathology. Overall, their results highlight Nitric Oxide Synthase 1 Adaptor Protein as a novel druggable disease-relevant gene in TAR DNA-binding protein 43 kDa-related proteinopathies.Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies

The Large Observatory For X-ray Timing: LOFT

LOFT, the Large Observatory for X-ray Timing, is a new space mission concept devoted to observations of Galactic and extra-Galactic sources in the X-ray domain with the main goals of probing gravity theory in the very strong field environment of black holes and other compact objects, and investigating the state of matter at supra-nuclear densities in neutron stars. The instruments on-board LOFT, the Large area detector and the Wide Field Monitor combine for the first time an unprecedented large effective area (~10 m2 at 8 keV) sensitive to X-ray photons mainly in the 2-30 keV energy range and a spectral resolution approaching that of CCD-based telescopes (down to 200 eV at 6 keV). LOFT is currently competing for a launch of opportunity in 2022 together with the other M3 mission candidates of the ESA Cosmic Vision Progra