Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation

Peer reviewedPublisher PD

The Role of HNRNPC-RARG in APL-like AML

https://openworks.mdanderson.org/sumexp22/1037/thumbnail.jp

Direct Determination of Multiple Ligand Interactions with the Extracellular Domain of the Calcium Sensing Receptor

Numerous in vivo functional studies have indicated that the dimeric extracellular domain (ECD) of the CaSR plays a crucial role in regulating Ca2+ homeostasis by sensing Ca2+ and L-Phe. However, direct interaction of Ca2+ and Phe with the receptor’s ECD and the resultant impact on its structure and associated conformational changes have been hampered by the large size of the ECD, its high degree of glycosylation, and the lack of biophysical methods to monitor weak interactions in solution. In the present study, we purified the glycosylated extracellular domain of CaSR (ECD) (residues 20~612), containing either complex or high mannose N-glycan structures depending on the host cell line employed for recombinant expression. Both glycosylated forms of the CaSR ECD were purified as dimers and exhibit similar secondary structures with ~50% -helix, ~20% -sheet content and a well buried Trp environment. Using various spectroscopic methods, we have shown that both protein variants bind Ca2+ with a Kd of 3.0~5.0 mM. The local conformational changes of the proteins induced by their interactions with Ca2+ were visualized by NMR with specific 15N Phe-labeled forms of the ECD. Saturation transfer difference (STD) NMR approaches demonstrated for the first time a direct interaction between the CaSR ECD and L-Phe. We further demonstrated that L-Phe increases the binding affinity of the CaSR ECD for Ca2+. Our findings provide new insights into the mechanisms by which Ca2+ and amino acids regulate the CaSR and may pave the way for exploration of the structural properties of CaSR and other members of family C of the GPCR superfamily

Model study on the photoassociation of a pair of trapped atoms into an ultralong-range molecule

Using the method of quantum-defect theory, we calculate the ultralong-range molecular vibrational states near the dissociation threshold of a diatomic molecular potential which asymptotically varies as $-1/R^3$. The properties of these states are of considerable interest as they can be formed by photoassociation (PA) of two ground state atoms. The Franck-Condon overlap integrals between the harmonically trapped atom-pair states and the ultralong-range molecular vibrational states are estimated and compared with their values for a pair of untrapped free atoms in the low-energy scattering state. We find that the binding between a pair of ground-state atoms by a harmonic trap has significant effect on the Franck-Condon integrals and thus can be used to influence PA. Trap-induced binding between two ground-state atoms may facilitate coherent PA dynamics between the two atoms and the photoassociated diatomic molecule.Comment: 11 pages, 4 figures, to appear in Phys. Rev. A (September, 2003

Phosphodiesterase-4D Knock-down in the Prefrontal Cortex Alleviates Chronic Unpredictable Stress-Induced Depressive-Like Behaviors and Memory Deficits in Mice

Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices

Nebular C IV 1550 Imaging of the Metal-Poor Starburst Mrk 71: Direct Evidence of Catastrophic Cooling

We use the Hubble Space Telescope ACS camera to obtain the first spatially resolved, nebular imaging in the light of C IV 1548,1551 by using the F150LP and F165LP filters. These observations of the local starburst Mrk 71 in NGC 2366 show emission apparently originating within the interior cavity around the dominant super star cluster (SSC), Knot A. Together with imaging in He II 4686 and supporting STIS FUV spectroscopy, the morphology and intensity of the C IV nebular surface brightness and the C IV / He II ratio map provide direct evidence that the mechanical feedback is likely dominated by catastrophic radiative cooling, which strongly disrupts adiabatic superbubble evolution. The implied extreme mass loading and low kinetic efficiency of the cluster wind are reasonably consistent with the wind energy budget, which is probably enhanced by radiation pressure. In contrast, the Knot B SSC lies within a well-defined superbubble with associated soft X-rays and He II 1640 emission, which are signatures of adiabatic, energy-driven feedback from a supernova-driven outflow. This system lacks clear evidence of C IV from the limb-brightened shell, as expected for this model, but the observations may not be deep enough to confirm its presence. We also detect a small C IV-emitting object that is likely an embedded compact H II region. Its C IV emission may indicate the presence of very massive stars (> 100 M_sun) or strongly pressure-confined stellar feedback.Comment: 13 pages, 8 figures. Accepted to ApJ Letter

The Enigmatic X-ray Point Sources at the Central Stars of NGC 6543 and NGC 7293

Recent Chandra ACIS-S observations have detected a point source at the central star of NGC 6543 and confirmed the point source nature of the hard X-ray emission from NGC 7293. The X-ray spectra of both sources peak between 0.5 keV and 1.0 keV and show line features indicating a thin plasma at temperatures of a few times 10^6 K. Their X-ray luminosities are 10^30 erg/s and 3x10^29 erg/s, respectively. We have considered four different mechanisms to explain the nature of these sources. The X-ray emission from the central star of NGC 6543 may originate from the coronal activity of an undetected companion star or from shocks in its fast stellar wind, while the hard X-ray emission from NGC 7293 might be ascribed to an undetected dMe companion. Follow-up observations are needed to determine the existence and natures of these stellar companions.Comment: 5 pages, 3 figures, accepted for publication in the ApJ