Endothelin 1-induced retinal ganglion cell death is largely mediated by JUN activation.

Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells (RGCs), the output neurons of the retina. Multiple lines of evidence show the endothelin (EDN, also known as ET) system is important in glaucomatous neurodegeneration. To date, the molecular mechanisms within RGCs driving EDN-induced RGC death have not been clarified. The pro-apoptotic transcription factor JUN (the canonical target of JNK signaling) and the endoplasmic reticulum stress effector and transcription factor DNA damage inducible transcript 3 (DDIT3, also known as CHOP) have been shown to act downstream of EDN receptors. Previous studies demonstrated that JUN and DDIT3 were important regulators of RGC death after glaucoma-relevant injures. Here, we characterized EDN insult in vivo and investigated the role of JUN and DDIT3 in EDN-induced RGC death. To accomplish this, EDN1 ligand was intravitreally injected into the eyes of wildtype, Six3-cre+Junfl/fl (Jun-/-), Ddit3 null (Ddit3-/-), and Ddit3-/-Jun-/- mice. Intravitreal EDN1 was sufficient to drive RGC death in vivo. EDN1 insult caused JUN activation in RGCs, and deletion of Jun from the neural retina attenuated RGC death after EDN insult. However, deletion of Ddit3 did not confer significant protection to RGCs after EDN1 insult. These results indicate that EDN caused RGC death via a JUN-dependent mechanism. In addition, EDN signaling is known to elicit potent vasoconstriction. JUN signaling was shown to drive neuronal death after ischemic insult. Therefore, the effects of intravitreal EDN1 on retinal vessel diameter and hypoxia were explored. Intravitreal EDN1 caused transient retinal vasoconstriction and regions of RGC and Müller glia hypoxia. Thus, it remains a possibility that EDN elicits a hypoxic insult to RGCs, causing apoptosis via JNK-JUN signaling. The importance of EDN-induced vasoconstriction and hypoxia in causing RGC death after EDN insult and in models of glaucoma requires further investigation

Presupernova Evolution with Improved Rates for Weak Interactions

Recent shell-model calculations of weak-interaction rates for nuclei in the mass range A = 45 - 65 have resulted in substantial revisions to the hitherto standard set of Fuller, Fowler, & Newman (FFN). In particular, key electron-capture rates, such as that for Co60 are much smaller. We consider here the effects of these revised rates on the presupernova (post-oxygen burning) evolution of massive stars in the mass range 11 to 40 M_sun. Moreover, we include, for the first time in models by our group, the effects of modern rates for beta-decay in addition to electron capture and positron emission. Values for the central electron mole number at the time of iron core collapse in the new models are typically larger, by delta Y_e = 0.005 to 0.015, than those of Woosley & Weaver 1995, with a tendency for the more massive models to display larger differences. About half of this change is a consequence of including beta-decay; the other half, result of the smaller rates for electron capture. Unlike what might be expected solely on basis of the larger Y_e's, the new iron core masses are systematically smaller owing to a decrease in the entropy in the outer iron core. The changes in iron core mass range from zero to 0.1 M_sun. We also observe, as predicted by Aufderheide et al. (1994), a tendency towards beta-equilibrium just prior to the collapse of the core, and the subsequent loss of that equilibrium as core collapse proceeds. We discuss the key weak reaction rates, both beta-decay and electron-capture, responsible for the evolution of Y_e and make suggestions for future measurements.Comment: 22 pages including 17 PostScript figures, uses emulateapj.sty, submitted to Ap

Extraction of thermal and electromagnetic properties in 45Ti

The level density and gamma-ray strength function of 45Ti have been determined by use of the Oslo method. The particle-gamma coincidences from the 46Ti(p,d gamma)45Ti pick-up reaction with 32 MeV protons are utilized to obtain gamma-ray spectra as function of excitation energy. The extracted level density and strength function are compared with models, which are found to describe these quantities satisfactorily. The data do not reveal any single-particle energy gaps of the underlying doubly magic 40Ca core, probably due to the strong quadruple deformation

Transcriptional control of retinal ganglion cell death after axonal injury.

Injury to the axons of retinal ganglion cells (RGCs) is a key pathological event in glaucomatous neurodegeneration. The transcription factors JUN (the target of the c-Jun N-terminal kinases, JNKs) and DDIT3/CHOP (a mediator of the endoplasmic reticulum stress response) have been shown to control the majority of proapoptotic signaling after mechanical axonal injury in RGCs and in other models of neurodegeneration. The downstream transcriptional networks controlled by JUN and DDIT3, which are critical for RGC death, however, are not well defined. To determine these networks, RNA was isolated from the retinas of wild-type mice and mice deficient in Jun, Ddit3, and both Jun and Ddit3 three days after mechanical optic nerve crush injury (CONC). RNA-sequencing data analysis was performed and immunohistochemistry was used to validate potential transcriptional signaling changes after axonal injury. This study identified downstream transcriptional changes after injury including both neuronal survival and proinflammatory signaling that were attenuated to differing degrees by loss of Ddit3, Jun, and Ddit3/Jun. These data suggest proinflammatory signaling in the retina might be secondary to activation of pro-death pathways in RGCs after acute axonal injury. These results determine the downstream transcriptional networks important for apoptotic signaling which may be important for ordering and staging the pro-degenerative signals after mechanical axonal injury

M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation

We show that the M2 isoform of pyruvate kinase (M2PYK) exists in equilibrium between monomers and tetramers regulated by allosteric binding of naturally occurring small-molecule metabolites. Phenylalanine stabilizes an inactive T-state tetrameric conformer and inhibits M2PYK with an IC(50) value of 0.24 mM, whereas thyroid hormone (triiodo-l-thyronine, T3) stabilizes an inactive monomeric form of M2PYK with an IC(50) of 78 nM. The allosteric activator fructose-1,6-bisphosphate [F16BP, AC(50) (concentration that gives 50% activation) of 7 μM] shifts the equilibrium to the tetrameric active R-state, which has a similar activity to that of the constitutively fully active isoform M1PYK. Proliferation assays using HCT-116 cells showed that addition of inhibitors phenylalanine and T3 both increased cell proliferation, whereas addition of the activator F16BP reduced proliferation. F16BP abrogates the inhibitory effect of both phenylalanine and T3, highlighting a dominant role of M2PYK allosteric activation in the regulation of cancer proliferation. X-ray structures show constitutively fully active M1PYK and F16BP-bound M2PYK in an R-state conformation with a lysine at the dimer-interface acting as a peg in a hole, locking the active tetramer conformation. Binding of phenylalanine in an allosteric pocket induces a 13° rotation of the protomers, destroying the peg-in-hole R-state interface. This distinct T-state tetramer is stabilized by flipped out Trp/Arg side chains that stack across the dimer interface. X-ray structures and biophysical binding data of M2PYK complexes explain how, at a molecular level, fluctuations in concentrations of amino acids, thyroid hormone, and glucose metabolites switch M2PYK on and off to provide the cell with a nutrient sensing and growth signaling mechanism

Search for Fingerprints of Tetrahedral Symmetry in 156Gd^{156}Gd

Theoretical predictions suggest the presence of tetrahedral symmetry as an explanation for the vanishing intra-band E2-transitions at the bottom of the odd-spin negative parity band in $^{156}Gd$. The present study reports on experiment performed to address this phenomenon. It allowed to determine the intra-band E2 transitions and branching ratios B(E2)/B(E1) of two of the negative-parity bands in $^{156}Gd$.Comment: presented by Q.T. Doan at XLII Zakopane School of Physics: Breaking Frontiers: Submicron Structures in Physics and Biology, May 2008. 5 pages, minor corrections. To be published in the proceeding

Neutrino Interactions in Hot and Dense Matter

We study the charged and neutral current weak interaction rates relevant for the determination of neutrino opacities in dense matter found in supernovae and neutron stars. We establish an efficient formalism for calculating differential cross sections and mean free paths for interacting, asymmetric nuclear matter at arbitrary degeneracy. The formalism is valid for both charged and neutral current reactions. Strong interaction corrections are incorporated through the in-medium single particle energies at the relevant density and temperature. The effects of strong interactions on the weak interaction rates are investigated using both potential and effective field-theoretical models of matter. We investigate the relative importance of charged and neutral currents for different astrophysical situations, and also examine the influence of strangeness-bearing hyperons. Our findings show that the mean free paths are significantly altered by the effects of strong interactions and the multi-component nature of dense matter. The opacities are then discussed in the context of the evolution of the core of a protoneutron star.Comment: 41 pages, 25 figure

Assessment of the composition and condition of animation cels made from cellulose acetate

Cellulose diacetate and cellulose triacetate cels from animated feature films in the collection of the Walt Disney Animation Research Library were tested by several analytical techniques in order to assess their composition and look for evidence of degradation. Triphenyl phosphate and a range of phthalate plasticizers were identified using pyrolysis-gas chromatography/mass spectrometry, which also showed evidence that evaporation of more volatile plasticizers may have occurred. Plasticizer content measurements by solvent extraction, found to be more accurate than volatile content data from thermogravimetric analysis, revealed there was less residual plasticizer in triacetate cels compared to diacetate cels. Gas chromatography/mass spectrometry, performed to quantify the acetyl content of cels after removal of plasticizers by solvent extraction, revealed some evidence for hydrolysis of the oldest cels, although the reduction could be related to original variations in acetate content from the polymer manufacturers. Use of Fourier-transform infrared spectroscopy to measure deacetylation of the cellulose acetate polymer based on the hydroxyl to carbonyl peak area ratio proved less satisfactory. Moreover, because the cels cannot be measured directly due to interference from plasticizers, non-invasive assessment of deacetylation using a portable instrument would be impossible. The results from this analytical survey provide an important point of reference against which long-term changes in cel composition can be monitored. © 2014 The J. Paul Getty Trust. Published by Elsevier Ltd. All rights reserved

Dorsal muscle group area and surgical outcomes in liver transplantation

Introduction Better measures of liver transplant risk stratification are needed. Our previous work noted a strong relationship between psoas muscle area and survival following liver transplantation. The dorsal muscle group is easier to measure, but it is unclear if they are also correlated with surgical outcomes. Methods Our study population included liver transplant recipients with a preoperative CT scan. Cross‐sectional areas of the dorsal muscle group at the T12 vertebral level were measured. The primary outcomes for this study were one‐ and five‐yr mortality and one‐yr complications. The relationship between dorsal muscle group area and post‐transplantation outcome was assessed using univariate and multivariate techniques. Results Dorsal muscle group area measurements were strongly associated with psoas area ( r  = 0.72; p < 0.001). Postoperative outcome was observed from 325 patients. Multivariate logistic regression revealed dorsal muscle group area to be a significant predictor of one‐yr mortality (odds ratio [ OR ] = 0.53, p = 0.001), five‐yr mortality ( OR  = 0.53, p < 0.001), and one‐yr complications ( OR  = 0.67, p = 0.007). Conclusion Larger dorsal muscle group muscle size is associated with improved post‐transplantation outcomes. The muscle is easier to measure and may represent a clinically relevant postoperative risk factor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109316/1/ctr12422.pd