ESR, ENDOR and TRIPLE resonance studies of the primary donor radical cation P960+ in the photosynthetic bacterium Rhodopseudomonas viridis

The light-induced radical cation of the primary electron donor P960+• in photosynthetic reaction centers from Rhodopseudomonas viridis has been investigated by ESR, ENDOR and TRIPLE techniques. Both the comparison with the cation radical of monomeric bacteriochlorophyll b (BChl b) and with molecular-orbital calculations performed on P960+• using the results of an X-ray structure analysis, consistently show an asymmetric distribution of the unpaired electron over the two BChl b molecules which constitute P960+•. The possible relevance of this result for the primary electron transfer step in the reaction center is briefly discussed

Optical and Infrared Spectroscopy

Contains research objectives and reports on one research project

Local surface structure and composition control the hydrogen evolution reaction on iron nickel sulfides

In order to design more powerful electrocatalysts, developing our understanding of the role of the surface structure and composition of widely abundant bulk materials is crucial. This is particularly true in the search for alternative hydrogen evolution reaction (HER) catalysts to replace platinum. We report scanning electrochemical cell microscopy (SECCM) measurements of the (111)‐crystal planes of Fe4.5Ni4.5S8, a highly active HER catalyst. In combination with structural characterization methods, we show that this technique can reveal differences in activity arising from even the slightest compositional changes. By probing electrochemical properties at the nanoscale, in conjunction with complementary structural information, novel design principles are revealed for application to rational material synthesis

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

Genetic risk prediction of atrial fibrillation

Background—Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods—To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10-3 to <1x10-8 in a prior independent genetic association study. Results—Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10-4) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10-3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). Conclusions—Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms

Elbow Ulnar Collateral Ligament Reconstruction Using the Novel Docking Plus Technique in 324 Athletes

BACKGROUND: This retrospective case series examined 324 athletes who received elbow ulnar collateral ligament (UCL) reconstruction by a single surgeon in a private practice over a 9-year period. The novel Docking Plus technique for elbow UCL reconstruction in 324 athletes provided good or excellent Conway score results in 88% of patients. The preponderance of previous studies examining UCL reconstruction outcomes were performed by surgeons at one of only three institutions (Andrews Institute, Hospital for Special Surgery, Kerlan Jobe Orthopedic Clinic). METHODS: Patients undergoing UCL reconstruction from November 2005 to December 2014 were identified and contacted with a mailed survey and phone call. These patients were given a subjective 19 question survey assessing their outcomes from surgery. RESULTS: The participants who responded to our survey were 90% male and 77% baseball players, 73% of which were pitchers. Of the baseball players who responded, 51.9% were in high school at the time of their surgery, 37% college, 6.5% minor leagues, and 2.2% in Major League Baseball. After surgery, 36% of survey responders returned to a higher level of competition than previously. For example, a high school athlete who had UCL reconstruction and went on to pitch in college. Further, 45% returned to the same level, and 7% returned to a lower level. Subjective satisfaction, was reported in 92% of responders and 97.2% reported that, having surgery was a good idea. Symptom onset in the responding athletes was 58.9% sudden, and 41.1% gradual. Overall, 90.9% of respondents returned to play in less than 1.5 years while 6.3% never were able to return. Re-tear occurred in 2.5% of patients, while 8.8% had subjective nerve dysfunction for at least 3 months following surgery. CONCLUSION: The Docking Plus technique can produce excellent subjective and objective results in athletes. Further study is warranted to see the effects of this procedure in other settings and determine which method of reconstruction or repair is superior

How the oxygen tolerance of a [NiFe]-hydrogenase depends on quaternary structure

‘Oxygen-tolerant’ [NiFe]-hydrogenases can catalyze H(2) oxidation under aerobic conditions, avoiding oxygenation and destruction of the active site. In one mechanism accounting for this special property, membrane-bound [NiFe]-hydrogenases accommodate a pool of electrons that allows an O(2) molecule attacking the active site to be converted rapidly to harmless water. An important advantage may stem from having a dimeric or higher-order quaternary structure in which the electron-transfer relay chain of one partner is electronically coupled to that in the other. Hydrogenase-1 from E. coli has a dimeric structure in which the distal [4Fe-4S] clusters in each monomer are located approximately 12 Å apart, a distance conducive to fast electron tunneling. Such an arrangement can ensure that electrons from H(2) oxidation released at the active site of one partner are immediately transferred to its counterpart when an O(2) molecule attacks. This paper addresses the role of long-range, inter-domain electron transfer in the mechanism of O(2)-tolerance by comparing the properties of monomeric and dimeric forms of Hydrogenase-1. The results reveal a further interesting advantage that quaternary structure affords to proteins

Wiring of Photosystem II to Hydrogenase for Photoelectrochemical Water Splitting.

In natural photosynthesis, light is used for the production of chemical energy carriers to fuel biological activity. The re-engineering of natural photosynthetic pathways can provide inspiration for sustainable fuel production and insights for understanding the process itself. Here, we employ a semiartificial approach to study photobiological water splitting via a pathway unavailable to nature: the direct coupling of the water oxidation enzyme, photosystem II, to the H2 evolving enzyme, hydrogenase. Essential to this approach is the integration of the isolated enzymes into the artificial circuit of a photoelectrochemical cell. We therefore developed a tailor-made hierarchically structured indium-tin oxide electrode that gives rise to the excellent integration of both photosystem II and hydrogenase for performing the anodic and cathodic half-reactions, respectively. When connected together with the aid of an applied bias, the semiartificial cell demonstrated quantitative electron flow from photosystem II to the hydrogenase with the production of H2 and O2 being in the expected two-to-one ratio and a light-to-hydrogen conversion efficiency of 5.4% under low-intensity red-light irradiation. We thereby demonstrate efficient light-driven water splitting using a pathway inaccessible to biology and report on a widely applicable in vitro platform for the controlled coupling of enzymatic redox processes to meaningfully study photocatalytic reactions.This work was supported by the U.K. Engineering and Physical Sciences Research Council (EP/H00338X/2 to E.R. and EP/G037221/1, nanoDTC, to D.M.), the UK Biology and Biotechnological Sciences Research Council (BB/K002627/1 to A.W.R. and BB/K010220/1 to E.R.), a Marie Curie Intra-European Fellowship (PIEF-GA-2013-625034 to C.Y.L), a Marie Curie International Incoming Fellowship (PIIF-GA-2012-328085 RPSII to J.J.Z) and the CEA and the CNRS (to J.C.F.C.). A.W.R. holds a Wolfson Merit Award from the Royal Society.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/jacs.5b0373

Stimulation of Adenosine A 3 Receptors in Cerebral Ischemia: Neuronal Death, Recovery, or Both?

The role of the adenosine A 3 receptor continues to baffle, and, despite an increasing number of studies, the currently available data add to, rather than alleviate, the existing confusion. The reported effects of adenosine A 3 receptor stimulation appear to depend on the pattern of drug administration (acute vs. chronic), dose, and type of the target tissue. Thus, while acute exposure to A 3 receptor agonists protects against myocardial ischemia, it is severely damaging when these agents are given shortly prior to cerebral ischemia. Mast cells degranulate when their A 3 receptors are stimulated. Degranulation of neutrophils is, on the other hand, impaired. While reduced production of reactive nitrogen species has been reported following activation of A 3 receptors in collagen-induced arthritis, the process appears to be enhanced in cerebral ischemia. Indeed, immunocytochemical studies indicate that both pre- and postischemic treatment with A 3 receptor antagonist dramatically reduces nitric oxide synthase in the affected hippocampus. Even more surprisingly, low doses of A 3 receptor agonists seem to enhance astrocyte proliferation, while high doses induce their apoptosis. This review concentrates on the studies of cerebral A 3 receptors and, based on the available evidence, discusses the possibility of adenosine A 3 receptor serving as an integral element of the endogenous cerebral neuroprotective complex consisting of adenosine and its receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75391/1/j.1749-6632.1999.tb07984.x.pd