Characterization of a Reductively-Activated Elimination Pathway Relevant to the Biological Chemistry of the Kinamycins and Lomaiviticins

The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling analyses, we show that kinamycin C (4) and the monomeric lomaiviticin aglycon (24) operate by a mechanism of action that is distinct from simple diazofluorenes, such as 23

CALIPSO Observations of Transatlantic Dust: Vertical Stratification and Effect of Clouds

CALIOP nighttime measurements of lidar backscatter, color and depolarization ratios during the summer of 2007 are used to study transatlantic dust properties downwind of Saharan sources, and to examine the interaction of clouds and dust. We discuss the following findings: (1) while lidar backscatter doesn't change much with altitude in the Saharan Air Layer (SAL), depolarization and color ratios both increase with altitude in the SAL; (2) lidar backscatter and color ratio increase as dust is transported westward in the SAL; (3) the vertical lapse rate of dust depolarization ratio increases within SAL as plumes move westward; (4) nearby clouds barely affect the backscatter and color ratio of dust volumes within SAL but not so below SAL. Finally, (5) the odds of CALIOP finding dust below SAL next to clouds are about 2/3 of those far away from clouds. This feature, together with an apparent increase in depolarization ratio near clouds, indicates that particles in some dusty volumes lose asphericity in the humid air near clouds, and cannot be identified by CALIPSO as dust

Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning.

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD(G521R). Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning

The Progenitor of Supernova 2004dj in a Star Cluster

The progenitor of type II-plateau supernova (SN) 2004dj is identified with a supergiant in a compact star cluster known as "Sandage Star 96" (S96) in the nearby spiral galaxy NGC 2403, which was fortuitously imaged as part of the Beijing-Arizona-Taiwan-Connecticut (BATC) Multicolor Sky Survey from Feb 1995 to Dec 2003 prior to SN 2004dj. The superior photometry of BATC images for S96, taken with 14 intermediate-band filters covering 3000-10000\AA, unambiguously establishes the star cluster nature of S96 with an age of $\sim 20$Myr, a reddening of $\hbox{E}(B-V)\sim 0.35$ mag and a total mass of $\sim 96,000$M$_{\odot}$. The compact star cluster nature of S96 is also consistent with the lack of light variations in the past decade. The SN progenitor is estimated to have a main-sequence mass of $\sim$12M$_{\odot}$. The comparison of our intermediate-band data of S96 with the post-outburst photometry obtained as the SN has significantly dimmed, may hopefully conclusively establish the nature of the progenitor.Comment: 4 pages; 3 figures. To accept for Publications in ApJ Letters, but slightly longer in this perprin

Loss of FKBP5 Affects Neuron Synaptic Plasticity: An Electrophysiology Insight

FKBP5 (FKBP51) is a glucocorticoid receptor (GR) binding protein, which acts as a co-chaperone of heat shock protein 90 (HSP90) and negatively regulates GR. Its association with mental disorders has been identified, but its function in disease development is largely unknown. Long-term potentiation (LTP) is a functional measurement of neuronal connection and communication, and is considered one of the major cellular mechanisms that underlies learning and memory, and is disrupted in many mental diseases. In this study, a reduction in LTP in Fkbp5 knockout (KO) mice was observed when compared to WT mice, which correlated with changes to the glutamatergic and GABAergic signaling pathways. The frequency of mEPSCs was decreased in KO hippocampus, indicating a decrease in excitatory synaptic activity. While no differences were found in levels of glutamate between KO and WT, a reduction was observed in the expression of excitatory glutamate receptors (NMDAR1, NMDAR2B and AMPAR), which initiate and maintain LTP. The expression of the inhibitory neurotransmitter GABA was found to be enhanced in Fkbp5 KO hippocampus. Further investigation suggested that increased expression of GAD65, but not GAD67, accounted for this increase. Additionally, a functional GABAergic alteration was observed in the form of increased mIPSC frequency in the KO hippocampus, indicating an increase in presynaptic GABA release. Our findings uncover a novel role for Fkbp5 in neuronal synaptic plasticity and highlight the value of Fkbp5 KO as a model for studying its role in neurological function and disease development

SN 2008S: A Cool Super-Eddington Wind in a Supernova Impostor

We present visual-wavelength photometry and spectroscopy of supernova SN2008S. Based on the low peak luminosity for a SN of M_R = -13.9 mag, photometric and spectral evolution unlike that of low-luminosity SNe, a late-time decline rate slower than 56Co decay, and slow outflow speeds of 600-1000 km/s, we conclude that SN2008S is not a true core-collapse SN and is probably not an electron-capture SN. Instead, we show that SN2008S more closely resembles a "SN impostor" event like SN1997bs, analogous to the giant eruptions of LBVs. Its total radiated energy was 1e47.8 ergs, and it may have ejected 0.05-0.2 Msun in the event. We discover an uncanny similarity between the spectrum of SN 2008S and that of the Galactic hypergiant IRC+10420, which is dominated by narrow H-alpha, [Ca II], and Ca II emission lines formed in an opaque wind. We propose a scenario where the vastly super-Eddington wind of SN2008S partly fails because of reduced opacity due to recombination, as suggested for IRC+10420. The range of initial masses susceptible to eruptive LBV-like mass loss was known to extend down to 20-25 Msun, but estimates for the progenitor of SN2008S (and the similar NGC300 transient) may extend this range to around 15 Msun. As such, SN2008S may have implications for the progenitor of SN1987A.Comment: 4.5 pages, 2 figs, ApJ Letters accepted, figs and text significantly revised, fig1 in colo

Evidence for Extremely High Dust Polarization Efficiency in NGC 3184

Recent studies have found the Type II-plateau supernova (SN) 1999gi to be highly polarized (p_max = 5.8%, where p_max is the highest degree of polarization measured in the optical bandpass; Leonard & Filippenko 2001) and minimally reddened (E[B-V] = 0.21 +/- 0.09 mag; Leonard et al. 2002). From multiple lines of evidence, including the convincing fit of a ``Serkowski'' interstellar polarization (ISP) curve to the continuum polarization shape, we conclude that the bulk of the observed polarization is likely due to dust along the line of sight (l-o-s), and is not intrinsic to SN 1999gi. We present new spectropolarimetric observations of four distant Galactic stars close to the l-o-s to SN 1999gi (two are within 0.02 degrees), and find that all are null to within 0.2%, effectively eliminating Galactic dust as the cause of the high polarization. The high ISP coupled with the low reddening implies an extraordinarily high polarization efficiency for the dust along this l-o-s in NGC 3184: ISP / E(B-V) = 31^{+22}_{-9} % mag^{-1}. This is inconsistent with the empirical Galactic limit (ISP / E[B-V] < 9% mag^{-1}), and represents the highest polarization efficiency yet confirmed for a single sight line in either the Milky Way or an external galaxy.Comment: 27 pages, accepted for publication by the Astronomical Journa

Optical and Near-Infrared Observations of the Highly Reddened, Rapidly Expanding Type Ia Supernova 2006X in M100

We present extensive optical (UBVRI), near-infrared (JK) light curves and optical spectroscopy of the Type Ia supernova (SN) 2006X in the nearby galaxy NGC 4321 (M100). Our observations suggest that either SN 2006X has an intrinsically peculiar color evolution, or it is highly reddened [E(B - V)_{host} = 1.42+/-0.04 mag] with R_V = 1.48+/-0.06, much lower than the canonical value of 3.1 for the average Galactic dust. SN 2006X also has one of the highest expansion velocities ever published for a SN Ia. Compared with the other SNe Ia we analyzed, SN 2006X has a broader light curve in the U band, a more prominent bump/shoulder feature in the V and R bands, a more pronounced secondary maximum in the I and near-infrared bands, and a remarkably smaller late-time decline rate in the B band. The B - V color evolution shows an obvious deviation from the Lira-Phillips relation at 1 to 3 months after maximum brightness. At early times, optical spectra of SN 2006X displayed strong, high-velocity features of both intermediate-mass elements (Si, Ca, and S) and iron-peak elements, while at late times they showed a relatively blue continuum, consistent with the blue U-B and B-V colors at similar epochs. A light echo and/or the interaction of the SN ejecta and its circumstellar material may provide a plausible explanation for its late-time photometric and spectroscopic behavior. Using the Cepheid distance of M100, we derive a Hubble constant of 72.7+/-8.2 km s^{-1} Mpc^{-1}(statistical) from the normalized dereddened luminosity of SN 2006X. We briefly discuss whether abnormal dust is a universal signature for all SNe Ia, and whether the most rapidly expanding objects form a subclass with distinct photometric and spectroscopic properties.Comment: 48 pages, 20 figures and 11 tables. Accepted Version (ApJ, 2008, March issue

Structural phase transitions in epitaxial perovskite films

Three different film systems have been systematically investigated to understand the effects of strain and substrate constraint on the phase transitions of perovskite films. In SrTiO$_3$ films, the phase transition temperature T$_C$ was determined by monitoring the superlattice peaks associated with rotations of TiO$_6$ octahedra. It is found that T$_C$ depends on both SrTiO$_3$ film thickness and SrRuO$_3$ buffer layer thickness. However, lattice parameter measurements showed no sign of the phase transitions, indicating that the tetragonality of the SrTiO$_3$ unit cells was no longer a good order parameter. This signals a change in the nature of this phase transition, the internal degree of freedom is decoupled from the external degree of freedom. The phase transitions occur even without lattice relaxation through domain formation. In NdNiO$_3$ thin films, it is found that the in-plane lattice parameters were clamped by the substrate, while out-of-plane lattice constant varied to accommodate the volume change across the phase transition. This shows that substrate constraint is an important parameter for epitaxial film systems, and is responsible for the suppression of external structural change in SrTiO$_3$ and NdNiO$_3$ films. However, in SrRuO$_3$ films we observed domain formation at elevated temperature through x-ray reciprocal space mapping. This indicated that internal strain energy within films also played an important role, and may dominate in some film systems. The final strain states within epitaxial films were the result of competition between multiple mechanisms and may not be described by a single parameter.Comment: REVTeX4, 14 figure