Cytotoxic Aggregation and Amyloid Formation by the Myostatin Precursor Protein

Myostatin, a negative regulator of muscle growth, has been implicated in sporadic inclusion body myositis (sIBM). sIBM is the most common age-related muscle-wastage disease with a pathogenesis similar to that of amyloid disorders such as Alzheimer's and Parkinson's diseases. Myostatin precursor protein (MstnPP) has been shown to associate with large molecular weight filamentous inclusions containing the Alzheimer's amyloid beta peptide in sIBM tissue, and MstnPP is upregulated following ER stress. The mechanism for how MstnPP contributes to disease pathogenesis is unknown. Here, we show for the first time that MstnPP is capable of forming amyloid fibrils in vitro. When MstnPP-containing Escherichia coli inclusion bodies are refolded and purified, a proportion of MstnPP spontaneously misfolds into amyloid-like aggregates as characterised by electron microscopy and binding of the amyloid-specific dye thioflavin T. When subjected to a slightly acidic pH and elevated temperature, the aggregates form straight and unbranched amyloid fibrils 15 nm in diameter and also exhibit higher order amyloid structures. Circular dichroism spectroscopy reveals that the amyloid fibrils are dominated by β-sheet and that their formation occurs via a conformational change that occurs at a physiologically relevant temperature. Importantly, MstnPP aggregates and protofibrils have a negative effect on the viability of myoblasts. These novel results show that the myostatin precursor protein is capable of forming amyloid structures in vitro with implications for a role in sIBM pathogenesis

The Infra‐Red Absorption Spectra of Ethylene and Tetra‐Deutero‐Ethylene under High Resolution

The fine structure of several infra‐red absorption bands of C2H4 and C2D4 have been resolved. From the rotational constants so found, the C☒C and C☒H distances in this molecule were calculated to be 1.353 and 1.071A, and the H☒C☒H angle to be 119°55′. An assignment of fundamental frequencies has been made which is consistent with the observed data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69770/2/JCPSA6-10-2-88-1.pd

Spectral Mapping Reconstruction of Extended Sources

Three dimensional spectroscopy of extended sources is typically performed with dedicated integral field spectrographs. We describe a method of reconstructing full spectral cubes, with two spatial and one spectral dimension, from rastered spectral mapping observations employing a single slit in a traditional slit spectrograph. When the background and image characteristics are stable, as is often achieved in space, the use of traditional long slits for integral field spectroscopy can substantially reduce instrument complexity over dedicated integral field designs, without loss of mapping efficiency -- particularly compelling when a long slit mode for single unresolved source followup is separately required. We detail a custom flux-conserving cube reconstruction algorithm, discuss issues of extended source flux calibration, and describe CUBISM, a tool which implements these methods for spectral maps obtained with ther Spitzer Space Telescope's Infrared Spectrograph.Comment: 11 pages, 8 figures, accepted by PAS

Demonstration of astrocytes in cultured amniotic fluid cells of three cases with neural-tube defect

We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4–80%) of RA cells cultured for 4–6 days by use of indirect immunofluorescence with GFA antiserum. Cells cultured from amniotic fluids of normal pregnancies and fetal fibroblasts were completely GFA protein negative. GFA protein is well established as a highly specific marker for astrocytes. Demonstration of astrocytes may prove to be a criterion of high diagnostic value for neural tube defects. The percentage of astrocytes decreased with increasing culture time, while the percentage of fibronectin positive cells increased both in amniotic fluid cell cultures from neural tube defects and normal pregnancies

Internal Dust Correction Factors for Star Formation Rates Derived for Dusty \HII Regions and Starburst Galaxies

Star formation rates in galaxies are frequently estimated using the Balmer line fluxes. However, these can be systematically underestimated because dust competes for the absorption of Lyman continuum photons in the ionized gas. Here we present theoretical correction factors in a simple analytic form. T These factors scale as the product of the ionization parameter, ${\cal U}$, and the nebular O/H abundance ratio, both of which can now be derived from the observation of bright nebular line ratios. The correction factors are only somewhat dependent upon the photoelectron production by grains, but are very sensitive to the presence of complex PAH-like carbonaceous molecules in the ionized gas, providing that these can survive in such an environment.Comment: 13 pages, 1 figures, Accepted for publication in ApJ. (Feb 1, 2003

Cooling glaciers in a warming climate since the Little Ice Age at Qaanaaq, northwest Kalaallit Nunaat (Greenland)

The centennial response of land-terminating glaciers in Greenland to climate change is largely unknown. Yet, such information is important to understand ongoing changes and for projecting the future evolution of Arctic subpolar glaciers, meltwater runoff, and sediment fluxes. This paper analyses the topography, geomorphology, and sedimentology of prominent moraine ridges and the proglacial areas of ice cap outlet glaciers on the Qaanaaq peninsula (Piulip Nunaa). We determine geometric changes of glaciers since the neoglacial maximum; the Little Ice Age (LIA), and we compare glacier behaviour during the LIA with that of the present day. There has been very little change in the rate of volume loss of each outlet glacier since the LIA compared with the rate between 2000 and 2019. However, the percentage of each glacier that is likely composed of cold-based ice has increased since the LIA, typically by 20%. The LIA moraines comprise subrounded, striated, and faceted clasts that evidence subglacial transport, and outwash plains, flutes, kames, and eskers that evidence subglacial motion and meltwater within temperate ice. Contrastingly, contemporary ice margins and their convex ice surfaces comprise pronounced primary foliation, ephemeral supraglacial drainage, sediment drapes from thrust plane fractures, and an absence of open crevasses and moulins. These calculations and observations together lead us to interpret that these outlet glaciers have transitioned towards an increasingly cold-based thermal regime despite a warming regional climate. Thermal regime transitions control glacier dynamics and therefore should be incorporated into glacier evolution models, especially where polythermal glaciers prevail and where climate is changing rapidly

Multiwavelength study of Cygnus A II. X-ray inverse-Compton emission from a relic counterjet and implications for jet duty-cycles

The duty-cycle of powerful radio galaxies and quasars such as the prototype Cygnus A is poorly understood. X-ray observations of inverse-Compton scattered Cosmic Microwave Background (ICCMB) photons probe lower Lorentz-factor particles than radio observations of synchrotron emission. Comparative studies of the nearer and further lobes, separated by many 10s of kpc and thus 10s of thousands of years in light-travel time, yield additional temporal resolution in studies of the lifecycles. We have co-added all archival Chandra ACIS-I data and present a deep 200 ks image of Cygnus A. This deep image reveals the presence of X-ray emission from a counterjet i.e. a jet receding from Earth and related to a previous episode of jet activity. The non-thermal X-ray emission, we interpret as ICCMB radiation. There is an absence of any discernible X-ray emission associated with a jet flowing towards Earth. We conclude that: (1) The emission from a relic jet, indicates a previous episode of jet activity, that took place earlier than the current jet activity appearing as synchrotron radio emission. (2) The presence of X-ray emission from a relic counterjet of Cygnus A and the absence of X-ray emission associated with any relic approaching jet constrains the timescale between successive episodes of jet activity to ~10^6 years. (3) Transverse expansion of the jet causes expansion losses which shifts the energy distribution to lower energies. (4) Assuming the electrons cooled due to adiabatic expansion, the required magnetic field strength is substantially smaller than the equipartition magnetic field strength. (5) A high minimum Lorentz factor for the distribution of relativistic particles in the current jet, of a few 10^3, is ejected from the central nucleus of this active galaxy. Abridged.Comment: Accepted for publication by MNRAS, 8 pages Dates in Table 1 correcte

The History and Future of the Local and Loop I Bubbles

The Local and Loop I superbubbles are the closest and best investigated supernova (SN) generated bubbles and serve as test laboratories for observations and theories of the interstellar medium. Since the morphology and dynamical evolution of bubbles depend on the ambient density and pressure distributions, a realistic modelling of the galactic environment is crucial for a detailed comparison with observations. We have performed 3D high resolution (down to 1.25 pc on a kpc-scale grid) hydrodynamic simulations of the Local Bubble (LB) and the neighbouring Loop I (L1) superbubble in a realistically evolving inhomogeneous background ISM, disturbed already by SN explosions at the Galactic rate for 200 Myr before the LB and L1 are generated. The LB is the result of 19 SNe occurring in a moving group, which passed through the present day local HI cavity. We can reproduce (i) the OVI column density in absorption within the LB in agreement with COPERNICUS and recent FUSE observations, giving N(OVI) <2 10^{13} cm^-2 and N(OVI)<7 10^{12} cm^-2, respectively, (ii) the observed sizes of the Local and Loop I superbubbles, (iii) the interaction shell between LB and L1, discovered with ROSAT, (iv) constrain the age of the LB to be 14.5+0.7/-0.4 Myr, (v) predict the merging of the two bubbles in about 3 Myr, when the interaction shell starts to fragment, (vi) the generation of blobs like the Local Cloud as a consequence of a dynamical instability. We find that evolving superbubbles strongly deviate from idealised self-similar solutions due to ambient pressure and density gradients, as well as due to turbulent mixing and mass loading. Hence, at later times the hot interior can break through the surrounding shell, which may also help to explain the puzzling energy "deficit" observed in LMC bubbles.Comment: Accepted for publication in Astronomy and Astrophysics Letters. The paper contains 5 pages and 11 figures. Fig. 1a replaced by correct figur

SN 2011ht: Confirming a Class of Interacting Supernovae with Plateau Light Curves (Type IIn-P)

We present photometry and spectroscopy of the Type IIn supernova (SN) 2011ht, identified previously as a SN impostor. The light curve exhibits an abrupt transition from a well-defined ~120 day plateau to a steep bolometric decline. Leading up to peak brightness, a hot emission-line spectrum exhibits signs of interaction with circumstellar material (CSM), in the form of relatively narrow P-Cygni features of H I and He I superimposed on broad Lorentzian wings. For the remainder of the plateau phase the spectrum exhibits strengthening P-Cygni profiles of Fe II, Ca II, and H-alpha. By day 147, after the plateau has ended, the SN entered the nebular phase, heralded by the appearance of forbidden transitions of [O I], [O II], and [Ca II] over a weak continuum. At this stage, the light curve exhibits a low luminosity that is comparable to that sub-luminous Type II-P supernovae, and a relatively fast visual-wavelength decline that is significantly steeper than the Co-56 decay rate. However, the total bolometric decline, including the IR luminosity, is consistent with Co-56 decay, and implies a low Ni-56 mass of ~0.01 M(Sun). We therefore characterize SN 2011ht as a bona-fide core-collapse SN very similar to the peculiar SNe IIn 1994W and 2009kn. These three SNe define a subclass, which are Type IIn based on their spectrum, but that also exhibit well-defined plateaus and produce low Ni-56 yields. We therefore suggest Type IIn-P as a name for this subclass. Possible progenitors of SNe IIn-P, consistent with the available data, include 8-10 M(Sun) stars, which undergo core collapse as a result of electron capture after a brief phase of enhanced mass loss, or more massive M>25 M(Sun) progenitors, which experience substantial fallback of the metal-rich radioactive ejecta. In either case, the energy radiated by these three SNe during their plateau must be dominated by CSM interaction (abridged).Comment: accepted, post-proof version (includes new data