Identification of diverse lipid-binding modes in the groove of zinc α2 glycoprotein reveals its functional versatility

ZAG is a multifunctional glycoprotein with a class I MHC-like protein fold and an α1-α2 lipid-binding groove. The intrinsic ZAG ligand is unknown. Our previous studies showed that ZAG binds the dansylated C11 fatty acid, DAUDA, differently to the boron dipyrromethane C16 fatty acid, C16-BODIPY. Here, the molecular basis for this difference was elucidated. Multi-wavelength analytical ultracentrifugation confirmed that DAUDA and C16-BODIPY individually bind to ZAG and compete for the same binding site. Molecular docking of lipid-binding in the structurally related CD1-proteins predicted nine conserved ligand contact residues in ZAG. Twelve mutants were accordingly created by alanine scanning site directed mutagenesis for characterisation. Mutation of Y12 caused ZAG to misfold. Mutation of K147, R157 and A158 abrogated C16-BODIPY but not DAUDA binding. L69 and T169 increased the fluorescence emission intensity of C16-BODIPY but not of DAUDA compared to wild-type ZAG and showed that C16-BODIPY binds close to T169 and L69. Distance measurements of the crystal structure revealed K147 forms a salt bridge with D83. A range of bioactive bulky lipids including phospholipids and sphingolipids displaced DAUDA from the ZAG binding site but unexpectedly did not displace C16-BODIPY. We conclude that the ZAG α1-α2 groove contains separate but overlapping sites for DAUDA and C16-BODIPY and is involved in binding to a bulkier and wider repertoire of lipids than previously reported. This work suggested that the in vivo activity of ZAG may be dictated by its lipid ligand

Incarcerated transmesosigmoid hernia presenting in a 60-year-old man: a case report

© 2008 Collins et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

On supersymmetric quantum mechanics

This paper constitutes a review on N=2 fractional supersymmetric Quantum Mechanics of order k. The presentation is based on the introduction of a generalized Weyl-Heisenberg algebra W_k. It is shown how a general Hamiltonian can be associated with the algebra W_k. This general Hamiltonian covers various supersymmetrical versions of dynamical systems (Morse system, Poschl-Teller system, fractional supersymmetric oscillator of order k, etc.). The case of ordinary supersymmetric Quantum Mechanics corresponds to k=2. A connection between fractional supersymmetric Quantum Mechanics and ordinary supersymmetric Quantum Mechanics is briefly described. A realization of the algebra W_k, of the N=2 supercharges and of the corresponding Hamiltonian is given in terms of deformed-bosons and k-fermions as well as in terms of differential operators.Comment: Review paper (31 pages) to be published in: Fundamental World of Quantum Chemistry, A Tribute to the Memory of Per-Olov Lowdin, Volume 3, E. Brandas and E.S. Kryachko (Eds.), Springer-Verlag, Berlin, 200

Adaptation to altered balance conditions in unilateral amputees due to atherosclerosis: a randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Amputation impairs the ability to balance. We examined adaptation strategies in balance following dysvascularity-induced unilateral tibial amputation in skilled prosthetic users (SPU) and first fitted amputees (FFA) (N = 28).</p> <p>Methods</p> <p>Excursions of center of pressure (COP) were determined during 20 s quiet standing using a stabilometry system with eyes-open on both legs or on the non-affected leg(s). Main measures: COP trajectories and time functions; distribution of reaction forces between the two legs; inclination angles obtained through second order regression analysis using stabilogram data.</p> <p>Results</p> <p>FFA vs SPU demonstrated 27.8% greater postural sway in bilateral stance (p = 0.0004). Postural sway area was smaller in FFA standing on the non-affected leg compared with SPU (p = 0.028). The slope of the regression line indicating postural stability was nearly identical in FFA and SPU and the direction of regression line was opposite for the left and right leg amputees.</p> <p>Conclusion</p> <p>Of the two adaptation strategies in balance, the first appears before amputation due to pain and fatigue in the affected leg. This strategy appears in the form of reduced postural sway while standing on the non-affected leg. The second adaptation occurs during rehabilitation and regular use of the prosthesis resulting in normal weightbearing associated with reduced postural sway on two legs and return to the normal postural stability on one leg.</p

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base