Structural analysis of site-directed mutants of cellular retinoic acid-binding protein II addresses the relationship between structural integrity and ligand binding

A water network stabilizes the structure of cellular retionic acid binding protein II

Anomalous sea-ice reduction in the Eurasian Basin of the Arctic Ocean during summer 2010

Special Issue: The Second International Symposium on the Arctic Research (ISAR - 2

Synthesis, Characterization, and Molecular Structure of Bis(tetraphenylcyclopentdienyl)rhodium(II)⊗

A 5 day diglyme reflux of Rh(acac)3 and K(C5HPh4), followed by treatment with aqueous HPF6, produces orange-yellow [(C5HPh4)2Rh]PF66 in 40 - 50% yield. Reduction of [(C5HPh4)2Rh]PF6 with sodium amalgam in THF yields olive green (C5HPh4)2Rh in 70% yield. (C5HPh4)2Rh crystallizes in the triclinic [Error : unloaded OLE object or mail attachment]space group with unit-cell parameters of a = 8.622 (3) Å, b = 10.778 (4) Å, c = 12.894 (5) Å, a = 65.58 (3)°, b = 72.66 (3)°, g = 83.52 (3)°, and Z = 1. The least squares data refined to RF = 7.63% and RwF = 10.12% for the 2479 independent observed reflections with Fo \u3e 5s(Fo ). The metal-centroid distance is 1.904 Å and all other bond lengths and angles are similar to known octaphenylmetallocenes. ESR spectra of (C5HPh4)2Rh in low-temperature glasses display a rhombic g-tensor with resolution of Rh hyperfine splitting on one-g-component. Analysis of the spectral parameters is consistent with a d7 configuration derived from a nearly degenerate dxz, dyz ground state. Voltammetry and coulometry establish the electron-transfer series (C5HPh4)2Rh1+/0/1- with E° values of -1.44 V and -2.13 V vs ferrocene. The heterogeneous charge transfer rate of the second reduction is about three orders of magnitude lower than that of the first

Use of Cholecystokinin to Prevent the Development of Parenteral Nutritionâ Associated Cholestasis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142290/1/jpen0100.pd

Toward An Understanding Of The Retinal Chromophore In Rhodopsin Mimics

Recently, a rhodopsin protein mimic was constructed by combining mutants of the cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal chromophore. Here, we present a combine computational quantum mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of CRABPII. We employ the QM/MM models to study the absorption (lambda(a)(max)), fluorescence (lambda(f)(max)), and reactivity of a CRABPII triple mutant incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also study the spectroscopy of the same mutant incorporating the unprotonated chromophore and of another double mutant incorporating the neutral unbound retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary fluorescence spectroscopy and ultrafast transient absorption spectroscopy resolved two different evolving excited state populations which were computationally assigned to distinct locally excited and charge-transfer species. This last species is shown to evolve along reaction paths describing a facile isomerization of the biologically relevant 11-cis and 13-cis double bonds. This work represents a first exploratory attempt to model and study these artificial protein systems. It also indicates directions for improving the QM/MM models so that they could be more effectively used to assist the bottom-up design of genetically encodable probes and actuators employing the retinal chromophore

Dynamical Renormalization Group Approach to Quantum Kinetics in Scalar and Gauge Theories

We derive quantum kinetic equations from a quantum field theory implementing a diagrammatic perturbative expansion improved by a resummation via the dynamical renormalization group. The method begins by obtaining the equation of motion of the distribution function in perturbation theory. The solution of this equation of motion reveals secular terms that grow in time, the dynamical renormalization group resums these secular terms in real time and leads directly to the quantum kinetic equation. We used this method to study the relaxation in a cool gas of pions and sigma mesons in the O(4) chiral linear sigma model. We obtain in relaxation time approximation the pion and sigma meson relaxation rates. We also find that in large momentum limit emission and absorption of massless pions result in threshold infrared divergence in sigma meson relaxation rate and lead to a crossover behavior in relaxation. We then study the relaxation of charged quasiparticles in scalar electrodynamics (SQED). While longitudinal, Debye screened photons lead to purely exponential relaxation, transverse photons, only dynamically screened by Landau damping lead to anomalous relaxation, thus leading to a crossover between two different relaxational regimes. We emphasize that infrared divergent damping rates are indicative of non-exponential relaxation and the dynamical renormalization group reveals the correct relaxation directly in real time. Finally we also show that this method provides a natural framework to interpret and resolve the issue of pinch singularities out of equilibrium and establish a direct correspondence between pinch singularities and secular terms. We argue that this method is particularly well suited to study quantum kinetics and transport in gauge theories.Comment: RevTeX, 40 pages, 4 eps figures, published versio

Recurrence after laparoscopic and open Nissen fundoplication

Background: Laparoscopic Nissen fundoplication as treatment for gastroesophageal reflux disease (GERD) in adults has a reported recurrence rate of 2–17%. We investigated the rates and mechanisms of failure after laparoscopic Nissen fundoplication in children. Methods: All patients who underwent a laparoscopic Nissen fundoplication for GERD and who subsequently required a redo Nissen were reviewed ( n = 15). The control group consisted of the most recent 15 patients who developed recurrent GER after an open Nissen, fundoplication. Results: Between 1994 and 2000, laparoscopic Nissen fundoplication was performed in 179 patients. Fifteen patients (8.7%) underwent revision. The mechanisms of failure were herniation in four patients, wrap dehiscence in four, a too-short wrap in three, a loosened wrap in two, and other reasons in two. The reoperation was performed laparoscopically in five patients (33%). The failure mechanisms were different in the open patients: eight were due to slipped wraps; three to dehiscences; and two to herniations. Conclusion: The failure rate after laparoscopic Nissen is acceptably low. A redo laparoscopic Nissen can be performed safely after an initial laparoscopic approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41361/1/464_2002_Article_8515.pd

Interpreting the Neutron's Electric Form Factor: Rest Frame Charge Distribution or Foldy Term?

The neutron's electric form factor contains vital information on nucleon structure, but its interpretation within many models has been obscured by relativistic effects. I demonstrate that, to leading order in the relativistic expansion of a constituent quark model, the Foldy term cancels exactly against a contribution to the Dirac form factor F_1 to leave intact the naive interpretation of G^n_E as arising from the neutron's rest frame charge distribution.Comment: 13 page

Structural, mechanistic and regulatory studies of serine palmitoyltransferase

SLs (sphingolipids) are composed of fatty acids and a polar head group derived from l-serine. SLs are essential components of all eukaryotic and many prokaryotic membranes but S1P (sphingosine 1-phosphate) is also a potent signalling molecule. Recent efforts have sought to inventory the large and chemically complex family of SLs (LIPID MAPS Consortium). Detailed understanding of SL metabolism may lead to therapeutic agents specifically directed at SL targets. We have studied the enzymes involved in SL biosynthesis; later stages are species-specific, but all core SLs are synthesized from the condensation of l-serine and a fatty acid thioester such as palmitoyl-CoA that is catalysed by SPT (serine palmitoyltransferase). SPT is a PLP (pyridoxal 5'-phosphate)-dependent enzyme that forms 3-KDS (3-ketodihydrosphingosine) through a decarboxylative Claisen-like condensation reaction. Eukaryotic SPTs are membrane-bound multi-subunit enzymes, whereas bacterial enzymes are cytoplasmic homodimers. We use bacterial SPTs (e. g. from Sphingomonas) to probe their structure and mechanism. Mutations in human SPT cause a neuropathy [HSAN1 (hereditary sensory and autonomic neuropathy type 1)], a rare SL metabolic disease. How these mutations perturb SPT activity is subtle and bacterial SPT mimics of HSAN1 mutants affect the enzyme activity and structure of the SPT dimer. We have also explored SPT inhibition using various inhibitors (e. g. cycloserine). A number of new subunits and regulatory proteins that have a direct impact on the activity of eukaryotic SPTs have recently been discovered. Knowledge gained from bacterial SPTs sheds some light on the more complex mammalian systems. In the present paper, we review historical aspects of the area and highlight recent key developments.</p