Structural and electronic models of the water oxidizing complex in the S 0 state of photosystem II: a density functional study

Large size (228 atom, 229 atom for protonated form) molecular models of the oxygen evolving complex of photosystem II (OEC), with a complete set of ligating aminoacids, the redox-active tyrosine YZ, and proton/water transfer channels terminating at the water oxidizing Mn/Ca cluster, are constructed based on the highest available resolution X-ray diffraction structures of the protein and our previous density functional theory (DFT) studies of isolated metal cluster model structures. Geometries optimized using the general gradient approximation (GGA) or hybrid density functionals are compared with high-resolution extended X-ray absorption fine structure (EXAFS) spectroscopic data and show that an antiferromagnetic configuration of the Mn centers in the cluster gives computed metal-metal distances in excellent agreement with experiment. The excitation energies predicted by time-dependent density functional theory (TDDFT) calculations for truncated 106 atom and 78 atom structures derived from the large models show that a previously proposed III-III-III-II oxidation pattern of the Mn atoms agrees very well with the X-ray absorption near-edge structure (XANES) observed for the S0 state of the OEC. This supports a "low" Mn oxidation state paradigm for the OEC, when a realistic protein imposed environment for the catalytic metal cluster is used in calculations. The probable protonation sites in the cluster and roles of the proton/water transfer channels are discussed in light of the computational results

Late outcome of mitral valve replacement with the Cross-Jones prosthesis 36 years after initial surgery

A 60 year-old woman with rheumatic mitral stenosis underwent re-replacement of Cross- Jones caged lens mitral valve prosthesis, 36 years after valve implantation. In 1968, she underwent mitral commissurotomy. In 1992, she had a stroke, and in July 2009 echocardiography revealed the malfunction of the prosthesis with pannus and reduced mitral prosthetic area < 1.0 cm2 with the elevated transprosthetic gradient of 30 mm Hg. To begin with, she did not approve of the reoperation. Finally, she consented to this therapeutic option. In October 2009 Medtronic prosthesis Advantage 27 was re-implanted. We report the longest period of working Cross-Jones mitral valve in the literature. (Cardiol J 2011; 18, 6: 698&#8211;700

Late diagnosis of congenital cardiovascular defect

Coarctation of the aorta (CoA) is a common congenital anomaly that is usually treated in infancy or childhood. Adult patients with coarctation have a high incidence of associated cardiac disorders, including valve diseases, atrial fibrillation and ischemic heart disease. Most patients with uncorrected CoA die before reaching the age of 50 from complications such as myocardial infarction, intracranial hemorrhage, congestive heart failure (HF), infective endocarditis or aortic dissection. We report the case of a 65 year-old woman admitted to hospital with symptoms of heart failure NYHA class IV. She had been treated for several years for refractory arterial hypertension and concomitant stenocardia (II CCS). The symptoms of HF had been increasing over several months. Outpatient echocardiography examination revealed significant, increasing mitral and tricuspid valve regurgitation with progressive left ventricular dysfunction. The patient was referred for surgical repair of the mitral and tricuspid valves. In-hospital echocardiography and angiography revealed descending aorta discontinuity at the level of the aortic isthmus. This congenital disease revealed during hospitalization was determined to be the underlying cause of all the symptoms the patient presented. Due to the clinical status of the patient, she was discharged from surgical procedures and put on medication. (Cardiol J 2012; 19, 2: 201&#8211;203

Stability and specificity of transmembrane domain self-association by mutagenesis and protein design

Stability and specificity of transmembrane domain self-association by In this thesis, I investigate the sequence dependence of homodimerization of the transmembrane domain of the pro-apoptotic C. elegans protein BNIP3. Using site directed mutagenesis and two assays for dimerization, I show that the tight association of the CeBNIP3 transmembrane domain relies on overlapping but distinct sets of residues depending on the assay: in membranes, the critical residues are N183xxSFxxxGxxxG 194, whereas in detergents, the key residues are S186FxxGxxxGxxxS 198. The small residue Ser 186, the bulky residue Phe 187, and small residues Gly 190 and Gly 194 play key roles in CeBNIP3 dimerization in both assays. However, CeBNIP3 TMD self-association in detergents, but not membranes, depends critically on Ser 198; self-association in lipid bilayers, but not detergents, depends on Asn 183. Comparison with the previously identified dimerization motif for the human BNIP3 ortholog (SHxxAlxxGlxxG) shows that the residues that drive CeBNIP3 dimerization in membranes are chemically similar to, but distinct from, those that drive HsBNIP3 association. To explore how interfacial BNIP3 residues determine dimer stability and specificity, I generated a combinatorial library from the CeBNIP3 and HsBNIP3 motifs, (STT)(H/N)xx(A/S)(I/F)xxG(I/A)xxG, and tested the hybrid sequences for dimerization. All combinations of interfacial residues support strong to extremely strong dimerization in membranes, suggesting that the two parental sequences adopt similar structures. Not all sequences form dimers in detergents, and dimerization propensity correlates weakly with sequence hydrophobicity. Manipulating the solvent conditions to enhance the hydrophobic effect increases dimerization of some sequences but not others. The CeBNIP3 and HsBNIP3 transmembrane domains form homodimers but not heterodimers in detergents. Hybrid motif sequences show differing propensities to form heterodimers with wildtype CeBNIP3 TMD and HsBNIP3 TMD: some hybrids discriminate, binding only one wildtype sequence, and some interact with both. My findings identify the sequence elements responsible for stability and specificity of BNIP3-type transmembrane domain dimerization. My results also show that the hydrophobicity of membrane spans strongly influences their behavior in detergent assays of protein-protein interactions. The demonstration that altering the aqueous solvent conditions can improve the stability of integral membrane proteins in detergents may be of general importance in membrane protein biochemistry

Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study

Polish Ministry of Science and Higher Education, Grant No. 0174/P01/2010/70; 504-06-011