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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim In a natural geochemical cycle, manganese-oxide minerals (MnOx) are principally formed through a microbial process, where a putative multicopper oxidase MnxG plays an essential role. Recent success in isolating the approximately 230 kDa, enzymatically active MnxEFG protein complex, has advanced our understanding of biogenic MnOxmineralization. Here, the kinetics of MnOxformation catalyzed by MnxEFG are examined using a quartz crystal microbalance (QCM), and the first electrochemical characterization of the MnxEFG complex is reported using Fourier transformed alternating current voltammetry. The voltammetric studies undertaken using near-neutral solutions (pH 7.8) establish the apparent reversible potentials for the Type 2 Cu sites in MnxEFG immobilized on a carboxy-terminated monolayer to be in the range 0.36–0.40 V versus a normal hydrogen electrode. Oxidative priming of the MnxEFG protein complex substantially enhances the enzymatic activity, as found by in situ electrochemical QCM analysis. The biogeochemical significance of this enzyme is clear, although the role of an oxidative priming of catalytic activity might be either an evolutionary advantage or an ancient relic of primordial existence.

Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of L-arginine into L-citrulline. NO is a free radical gas with a short half-life in vivo (approximate to 5 s), therefore direct NO quantification is challenging. An indirect method - based on quantifying conversion of an L-Arg - to L-Cit-derivative by H-1 NMR spectroscopy is herein proposed. A small library of pyridyl containing L-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a-j and 11a-c were better or equivalent substrates for the eNOS enzyme (NO2- production = 19-46 uM) than native L-Arg (NO2- production = 25 mu M). Enzymatic conversion of L-Arg to L-Cit derivatives could be monitored by 1H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo. (C) 2017 The Authors. Published by Elsevier Ltd.

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The scalable synthesis of highly transparent and robust sub-monolayers of Co3O4 nano-islands, which efficiently catalyze water oxidation, is reported. Rapid aerosol deposition of Co3O4 nanoparticles and thermally induced self-organization lead to an ultra-fine nano-island morphology with more than 94% light transmission at a wavelength of 500 nm. These transparent sub-monolayers demonstrate a remarkable mass-weighted water oxidation activity of 2070–2350 A gCo3O4−1 and per-metal turnover frequency of 0.38–0.62 s−1 at an overpotential of 400 mV in 1 m NaOH aqueous solution. This mixed valent cobalt oxide structure exhibits excellent long-term electrochemical and mechanical stability preserving the initial catalytic activity over more than 12 h of constant current electrolysis and 1000 consecutive voltammetric cycles. The potential of the Co3O4 nano-islands for photoelectrochemical water splitting has been demonstrated by incorporation of co-catalysts in GaN nanowire photoanodes. The Co3O4-GaN photoanodes reveal significantly reduced onset overpotentials, improved photoresponse and photostability compared to the bare GaN ones. These findings provide a highly performing catalyst structure and a scalable synthesis method for the engineering of efficient photoanodes for integrated solar water-splitting cells.

We propose a new method for detecting conserved RNA secondary structures in a family of related RNA sequences. Our method is based on a combination of thermodynamic structure prediction and phylogenetic comparison. In contrast to purely phylogenetic methods, our algorithm can be used for small data sets of approximately 10 sequences, efficiently exploiting the information contained in the sequence variability. The procedure constructs a prediction only for those parts of sequences that are consistent with a single conserved structure. Our implementation produces reasonable consensus structures without user interference. As an example we have analysed the complete HIV-1 and hepatitis C virus (HCV) genomes as well as the small segment of hantavirus. Our method confirms the known structures in HIV-1 and predicts previously unknown conserved RNA secondary structures in HCV.

The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulphate ester, unsulphated cholecystokinin octapeptide and their fragments were tested on the dopamine, norepinephrine and serotonin contents of the rat hypothalamus, mesencephalon, amygdala, septum, cerebral cortex and striatum, as well as on the plasma corticosterone level. Cholecystokinin octapeptide sulphate ester and the tyrosine-sulphate-methionine and tyrosine-sulphate-methionine-glycine fragments increased the dopamine and norepinephrine contents of the hypothalamus and mesencephalon. The same compounds increased the dopamine content of the amygdala, while they decreased the dopamine and norepinephrine concentrations in the striatum. The plasma corticosterone level was also increased. The unsulphated cholecystokinin octapeptide and its fragments had no effects on the brain monoamine contents and slight but not significant effect on the plasma corticosterone level. The data suggest that the presence of the tyrosine-sulphate-methionine dipeptide is essential in the effects of cholecystokinin octapeptide sulphate ester on the monoamine contents of different brain areas, as well as on the plasma corticosterone level.

Chronic treatment with des-enkephalin-γ-endorphin (DEγE, β-endorphin 6–17) twice daily for 10 days into the nucleus accumbens of rats resulted in hypoactivity, while similar treatment with γ-endorphin antiserum led to a marked hyperactivity. This enhanced activity persisted for at least 3 days following discontinuation of treatment. Rats chronically treated with γ-endorphin antiserum into the nucleus accumbens habituated at a slower rate when tested repeatedly for locomotor activity, as well as for nociception. Passive avoidance behaviour was attenuated in the treated rats, when they were trained during treatment, but not when the learning trial was given before treatment and testing was performed during treatment. Treatment with γ-endorphin antiserum did not affect the diurnal rhythm in locomotion, the responsiveness to nociceptive stimulation and the basal and novelty stress induced-plasma corticosteroid levels. It is concluded that chronic treatment with γ-endorphin antiserum into the nucleus accumbens, which may lead to bio-inactivation of γ-type endorphins, causes hyperactivity and disturbances in habituation and cognitive functions. It is suggested that γ-type endorphins are physiologically involved in the control of distinct dopaminergic systems in the nucleus accumbens. The findings are discussed in relation to the role of mesolimbic dopaminergic systems in schizophrenic psychosis.

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The concentration of dopamine, norepinephrine, epinephrine and serotonin was determined in 6 rostrocaudal segments of the median eminence, 2 segments in the pituitary stalk, in the retrochiasmatic area and the pituitary lobes by radioenzymatic microassay in adult rats. The level of dopamine and norepinephrine was measured separately in the medial and lateral portions of the median eminence. All four amines measured were found unevenly distributed inside the median eminence: 1. the highest dopamine level was detected in the middle-caudal portions of the median eminence and in the rostral parts of the pituitary stalk; 2. high norepinephrine concentration was found in the retrochiasmatic area and this gradually diminished caudalwards; 3. relatively high epinephrine level was present in the rostral median eminence and retrochiasmatic area, but that in the caudal median eminence and pituitary stalk was low; 4. the level of serotonin increased caudalwards and showed a highest value in the caudal portion of the pituitary stalk. Relatively high dopamine and serotonin levels were also detectable in all three pituitary lobes where the concentration of norepinephrine was low and that of epinephrine was undetectable.

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0–6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1–5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p=0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.

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