Impact of Structure, Coupling Scheme, and State of Interest on the Energy Transfer in CP29.

The Qy and Bx excitation energy transfer (EET) in the minor light-harvesting complex CP29 (LHCII B4.1) antenna complex of Pisum sativum was characterized using a computational approach. We applied Förster resonance energy transfer (FRET) and the transition density cube (TDC) method to estimate the Coulombic coupling, based on a combination of classical molecular dynamics and quantum mechanics/molecular mechanics calculations. Employing TDC instead of FRET mostly affects the EET between chlorophylls (Chls) and carotenoids (Crts), as expected due to the Crts being spatially more challenging for FRET. Only between Chls, effects are found to be small (about only 0.1 EET efficiency change when introducing TDC instead of FRET). Effects of structural sampling were found to be small, illustrated by a small average standard deviation for the Qy state coupling elements (FRET/TDC: 0.97/0.94 cm-1). Due to the higher flexibility of the Bx state, the corresponding deviations are larger (FRET/TDC between Chl-Chl pairs: 17.58/22.67 cm-1, between Crt-Chl pairs: 62.58/31.63 cm-1). In summary, it was found for the Q band that the coupling between Chls varies only slightly depending on FRET or TDC, resulting in a minute effect on EET acceptor preference. In contrast, the coupling in the B band spectral region is found to be more affected. Here, the S2 (1Bu) states of the spatially challenging Crts may act as acceptors in addition to the B states of the Chls. Depending on FRET or TDC, several Chls show different Chl-to-Crt couplings. Interestingly, the EET between Chls or Crts in the B band is found to often outcompete the corresponding decay processes. The individual efficiencies for B band EET to Crts vary however strongly with the chosen coupling scheme (e.g., up to 0.29/0.99 FRET/TDC efficiency for the Chl a604/neoxanthin pair). Thus, the choice of the coupling scheme must involve a consideration of the state of interest.

Effect of protein matrix on CP29 spectra and energy transfer pathways.

We investigate energy transfer pathways between strongly coupled chlorophylls (Chls) in the CP29 (LHCII B4.1) antenna complex of Pisum sativum, including the possibility of higher energy states. We test for the environmental effects caused by the protein, membrane and solvent using a hybrid QM/MM approach. Classical molecular dynamics simulations of the full CP29 complex embedded in a DOPC membrane have been performed, followed by calculations of the time dependent DFT spectra of all Chls at several timesteps. The relative orientations of transition dipole moments (TDMs) were specifically analyzed, including and excluding the point charge field (PCF) of the surrounding environment. The PCF is found to drastically shift the spectra of specific Chls, while the majority of Chls is mostly unaffected. The net effect on the sum spectrum is however found to be negligible: The few strong changes in Chl spectra cancel each other due to being opposite in sign. We further find that the spectra of the Chls coordinating to water show a blue shift upon introduction of the environment. Conversely, the spectra of the Chls coordinating to glutamine show a red shift upon activation of the PCF. As the main influence of the PCF for tuning the couplings, we identify the energetic position of the individual chromophores. The fine-tuning, especially for states energetically above the Qy state, is however controlled by the changes in the TDM orientations. We also find an indication for the PCF to steer potentially harmful high energy excitations away from the PSII core complex.

Two-dimensional self-assembly of benzotriazole on an inert substrate.

The ultra-high vacuum (UHV) room temperature adsorption of benzotriazole (BTAH), a well-known corrosion inhibitor for copper, has been investigated on the pristine Au(111) surface using a combination of surface sensitive techniques. The dimensionality of the molecule is reduced from the 3D crystal structure to a 2-dimensional surface confinement, which induces the formation of hydrogen bonded 1-dimensional molecular chains consisting of alternating pro-S and pro-R enantiomers mainly. The 0-dimensional system is characteristic of gas-phase BTAH, which undergoes a tautomeric equilibrium, with consequences for the resulting adsorbed species. The balance between hydrogen bonding, inter-chain van der Waals interactions and surface-molecule interactions, and the correlation with the dimensionality of the system, are discussed in light of the experimental results and a computational description of the observed features.

Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease.

BACKGROUND AND AIMS: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis. PATIENTS AND METHODS: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation. RESULTS: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls. CONCLUSION: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.

Plasma pro-brain natriuretic peptides are strong biochemical markers in clinical cardiology.

The cardiac natriuretic peptides constitute a family of peptides that regulate fluid homeostasis as well as vascular tonus and growth. Following the fundamental establishment of the heart as an endocrine organ in the early 1980's, the cardiac natriuretic peptides have today been identified as potent biochemical tools in diverse aspects of clinical cardiology including as diagnostic, therapeutic and prognostic markers of cardiac dysfunction as well as potential drug targets. In man, Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are mainly synthesised and secreted by the failing heart, whereas the closely related C-type Natriuretic Peptide (CNP) appears to be a local factor secreted by the endothelium and hence is not considered as a cardiac natriuretic peptide. With the ongoing development of sensitive immunoassays, increased plasma concentrations of ANP and BNP peptides have been associated to a variety of cardiac diseases--but their clinical usefulness as biochemical markers in congestive heart failure is the most promising. In contrast to the large quantity of clinical research on cardiac-derived peptides, the basic understanding of the molecular heterogeneity of these peptides is however still insufficient. Since much clinical work on peptides derived from the proBNP precursor has been published recently, this mini-review will focus on these novel peptides and their potential applications in the clinical setting.

[Acquired warfarin resistance in a patient with mechanical heart valve]. / Erhvervet warfarinresistens hos en patient med mekanisk mitralklap.

We present a case report of a 37-year-old man with a mechanical mitral valve, who, presumably because of malabsorption, developed resistance to oral anticoagulant therapy. The patient was then treated with a replacement of the mechanical valve to biological valves, thereby eliminating the need for anticoagulant therapy. Our case report summarises the diagnostic approach to elucidate apparent resistance to anticoagulant therapy.

Follow-up of volar plate interposition arthroplasty (Tupper) of the metacarpophalangeal joints in rheumatoid hands: preliminary findings.

We present the results of a three-year follow-up study of 59 interposition volar plate arthroplasties (Tupper) on metacarpophalangeal joints in 13 patients with erosive rheumatoid arthritis. The median age at the time of operation was 60 years (range 45-77). All patients reported lasting pain relief at rest. Improvement of hand function was, however, less satisfactory as both grip and pinch strength were compromised in all patients. Seven patients were satisfied with the outcome whereas six complained of stiffness in the operated joints. All but one patient concluded that they would have the operation again if necessary.

Displaced chromatographic elution of gastrin-17 in normal human serum.

Sulfated gastrin-17 elutes by gel chromatography significantly earlier after incubation in human serum (KD: 0.48) than when added to buffer (KD: 0.62). Also, the elution of non-sulfated gastrin-17 changes after serum incubation although to a lesser extent (KD: 0.68 vs. 0.74). In contrast neither the N-terminal 1-13 nor the sulfated C-terminal hexapeptide fragment of gastrin-17 change elution positions after serum incubation. The earlier elution is concentration dependent. The results suggest that displaced elution of sulfated gastrin-17 may constitute part of the abundance of gastrin-34-like material in normal human serum. Hence, present concepts of gastrin heterogeneity in serum seem to require re-evaluation.

Effects of induction and age-dependent enzyme expression on lung bioavailability, metabolism, and DNA binding of urban air particulate-absorbed benzo[a]pyrene, 2-nitrofluorene, and 3-amino-1,4-dimethyl-5H-pyridol-(4,3)-indole.

The effect of interactions between urban air particulates (UAP) and carcinogens on bioavailability, metabolism, and DNA binding was studied in the isolated perfused and ventilated rat lung. The availability of benzo[a]pyrene (B[a]P) varied from 29 to 60% after intratracheal doses of carcinogen particulates dissolving extremely slow and fast, respectively. Several cytochrome P450 enzyme (P450) inducers acting as 2,3,7,8-tetrachlorodibenzo[p]dioxin-receptor ligands have been identified in UAP extracts. beta-Naphthoflavone (BNF) was used to study how P450 induction alters the lung metabolism of carcinogens. Pretreatment increased the lung clearance for B[a]P 8-fold and for 2-nitrofluorene (2NF) by a factor of four from 0.55 +/- 0.06 ml/min to 2.37 +/- 0.62 ml/min. Studies with the intact lung and with isolated lung cells show that carcinogen metabolism and pharmacokinetics depend both on the route of exposure and dosage and on the distribution of specific enzymes. A cytochrome P450IIB1 enzyme was detected in lung epithelial cells where it catalyzes 9-hydroxylation of 2NF. This rat lung 2NF-9-hydroxylation capacity increases in parallel with the age dependent up-regulation of lung P450IIB1 expression. Both human and rat lung tissue have the capacity to form 9-hydroxy-2-nitrofluorene (9-OH-2NF) that is mutagenic. A BNF-inducible P450IA1 was detected in endothelial and alveolar type II cells. Consequently, aromatic hydroxylation dominated when 2NF was dosed directly into the lung circulation. Pretreatment of rats with BNF before intratracheal B[a]P dosage induced lung cytochrome P450IA1. The 7,8-dihydroxy-9,10-oxybenzo[a]pyrene-deoxyguanosine adduct and the total lung DNA adduct levels increased significantly from a peak level of 75 +/- 8 to 151 +/- 19 fmole/mg DNA in lungs from control and BNF pretreated rats, respectively. 3-Amino-1,4-dimethyl-5H-pyridol-(4,3)-indole (TRP-P1) is a potent mutagen and carcinogen identified in UAP extracts. Dietary BNF pretreatment of rats altered the [14C]TRP-P1 distribution as analyzed by whole-body autoradiography. An enhanced retention was observed in the small intestine, forestomach, esophagus, and lung. UAP catalyzes oxygen radical formation and deoxyguanosine-8-hydroxylation, which were inhibited when the UAP samples were extracted with organic solvents or when they were incubated in the presence of desferroxamine. We therefore postulate that a polycyclic aromatic hydrocarbon autooxidation pathway may be responsible for generation of hydrogen peroxide, which may be further converted to hydroxyl radicals through an iron-dependent reaction.