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131.
Carlo dela Se?a Sureshbabu Narayanasamy Kenneth M. Riedl Robert W. Curley Jr. Steven J. Schwartz Earl H. Harrison 《The Journal of biological chemistry》2013,288(52):37094-37103
Humans cannot synthesize vitamin A and thus must obtain it from their diet. β-Carotene 15,15′-oxygenase (BCO1) catalyzes the oxidative cleavage of provitamin A carotenoids at the central 15–15′ double bond to yield retinal (vitamin A). In this work, we quantitatively describe the substrate specificity of purified recombinant human BCO1 in terms of catalytic efficiency values (kcat/Km). The full-length open reading frame of human BCO1 was cloned into the pET-28b expression vector with a C-terminal polyhistidine tag, and the protein was expressed in the Escherichia coli strain BL21-Gold(DE3). The enzyme was purified using cobalt ion affinity chromatography. The purified enzyme preparation catalyzed the oxidative cleavage of β-carotene with a Vmax = 197.2 nmol retinal/mg BCO1 × h, Km = 17.2 μm and catalytic efficiency kcat/Km = 6098 m−1 min−1. The enzyme also catalyzed the oxidative cleavage of α-carotene, β-cryptoxanthin, and β-apo-8′-carotenal to yield retinal. The catalytic efficiency values of these substrates are lower than that of β-carotene. Surprisingly, BCO1 catalyzed the oxidative cleavage of lycopene to yield acycloretinal with a catalytic efficiency similar to that of β-carotene. The shorter β-apocarotenals (β-apo-10′-carotenal, β-apo-12′-carotenal, β-apo-14′-carotenal) do not show Michaelis-Menten behavior under the conditions tested. We did not detect any activity with lutein, zeaxanthin, and 9-cis-β-carotene. Our results show that BCO1 favors full-length provitamin A carotenoids as substrates, with the notable exception of lycopene. Lycopene has previously been reported to be unreactive with BCO1, and our findings warrant a fresh look at acycloretinal and its alcohol and acid forms as metabolites of lycopene in future studies. 相似文献
132.
Many behavioural aspects of Anoplius infuscatus (Vander Linden) and Episyron sp. Schioedte were examined in detail, both on a qualitative and, when possible, on a quantitative level, during a long-term field study in Northern Italy. Both wasps dig unicellular nests on bare soil, which are filled with a single spider to feed the brood. The main differences regard the way to hunt their prey, that of burrowing, that of transporting and introducing the spider into the nest, the habit of amputating spider legs and the abdominal movements during nest closing. On the whole, starting from prey capture to nest closure, A. infuscatus is significantly slower than Episyron. The observed ethological differences are well fitted to the exploitation of the different preys consisting in wolf spiders (Lycosidae) and orb weaving spiders (Araneidae), respectively. Some flexibility in the observed behaviour is described. A critical re-examination of the literature shows that, even if most results agree with those of previous authors, two controversial points remain open regarding Episyron species: the position of the egg (on the prey or on the cell wall) and the way to grasp the spider during tranport and introdution into the nest. 相似文献
133.
Capsule Clutches of hole-nesting passerines suffer less predation if nestboxes are moved by 800–3000 m. Aims To see if Pine Marten predation upon clutches of insectivorous birds increases with the age of nestboxes and to see if predation is affected by the distance nestboxes are relocated from the plots where predation occurred the previous year. Methods The study was undertaken in two habitats of central Italy (deciduous and Holm Oak wood). In each habitat, nestboxes were placed and relocated in order to have plots with: new (first year of placement) or old (second year of placement) nestboxes; short (100 m) or long-distance (800–3000 m) relocated nestboxes following previous predation. Results After controlling for habitat, hole-nester density, competition with snakes and nestbox age, the plots with nestboxes replaced at a short distance from the original location suffered higher predation pressure. Pine Marten predation was higher in plots with older nestboxes. A high predation rate was observed in nestboxes replaced in plots where they had not been present for one year and where they had been heavily preyed on in past years. Conclusion To reduce the risks of predation by mammals, the relocation of old nestboxes should be carried out at a long distance from plots where predation had previously occurred. 相似文献
134.
Benjamin D. Stevens John Litchfield Jeffrey A. Pfefferkorn Karen Atkinson Christian Perreault Paul Amor Kevin Bahnck Martin A. Berliner Jessica Calloway Anthony Carlo David R. Derksen Kevin J. Filipski Mike Gumkowski Charanjeet Jassal Margit MacDougall Brendan Murphy Paul Nkansah John Pettersen Yan Zhang 《Bioorganic & medicinal chemistry letters》2013,23(24):6588-6592
Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. 相似文献
135.
Maria Maddalena Cavalluzzi Maurizio Viale Claudio Bruno Alessia Carocci Alessia Catalano Antonio Carrieri Carlo Franchini Giovanni Lentini 《Bioorganic & medicinal chemistry letters》2013,23(17):4820-4823
Lubeluzole, a neuroprotective anti-ischemic drug, and its enantiomer were prepared following a convenient procedure based on hydrolytic kinetic resolution. The ee values were >99% and 96%, respectively, as assessed by HPLC analysis. The chemosensitizing effects of both enantiomers were evaluated in combination with either doxorubicin (human ovarian adenocarcinoma A2780 cells) or paclitaxel (human lung carcinoma A549 cells) by the MTT assay. At the lowest concentrations used, lubeluzole showed an overall and remarkable tendency to synergize with both anticancer drugs. In ovarian cancer cells a clear prevalence of antagonistic effect was observed for the R-enantiomer. The synergistic effects of lubeluzole for both drugs were observed over a wide concentration window (0.005–5 μM), the lowest limit being at least 40 times lower than human plasma concentrations previously reported as causing serious side effects. 相似文献
136.
Annamaria Sinisi Barbara Calcinai Carlo Cerrano Henny A. Dien Angela Zampella Claudio D’Amore Barbara Renga Stefano Fiorucci Orazio Taglialatela-Scafati 《Bioorganic & medicinal chemistry》2013,21(17):5332-5338
Chemical investigation of an Indonesian specimen of Theonella swinhoei afforded the new dimeric macrolides isoswinholide B (5) and swinholide K (6), along with the known swinholides A (1), B (2) and D (3) and isoswinholide A (4). Isoswinholide B showed an unprecedented 21/19′ lactonization pattern, while swinholide K included an sp2 methylene attached at C-4 and an additional oxymethine group at C-5, whose configuration has been determined through application of J-based configuration analysis. The isolated swinholides (1–6), with the exception of isoswinholide B, showed a cytotoxic activity on HepG2 (hepatocarcinoma cell line) in the nanomolar range. 相似文献
137.
Marta Coll Philippe Cury Ernesto Azzurro Michel Bariche Giorgos Bayadas Jose Maria Bellido Christian Chaboud Joachim Claudet Abdel-Fattah El-Sayed Didier Gascuel Leyla Knittweis Carlo Pipitone Yianna Samuel-Rhoads Said Taleb Sergi Tudela Audrey Valls 《Reviews in Fish Biology and Fisheries》2013,23(4):415-434
138.
Hisham Mohammed Clive D’Santos Aurelien A. Serandour H. Raza Ali Gordon D. Brown Alan Atkins Oscar M. Rueda Kelly A. Holmes Vasiliki Theodorou Jessica L.L. Robinson Wilbert Zwart Amel Saadi Caryn S. Ross-Innes Suet-Feung Chin Suraj Menon John Stingl Carlo Palmieri Carlos Caldas Jason S. Carroll 《Cell reports》2013,3(2):342-349
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139.
Aldo Ragazzoni Cornelia Pirulli Domenica Veniero Matteo Feurra Massimo Cincotta Fabio Giovannelli Roberta Chiaramonti Mario Lino Simone Rossi Carlo Miniussi 《PloS one》2013,8(2)
Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders. 相似文献
140.
Maria A. De Marco Stefano Porru Paolo Cordioli Bruno M. Cesana Ana Moreno Laura Calzoletti Lebana Bonfanti Arianna Boni Antonio Scotto Di Carlo Cecilia Arici Angela Carta Maria R. Castrucci Isabella Donatelli Paola Tomao Vittoria M. Peri Livia Di Trani Nicoletta Vonesch 《PloS one》2013,8(2)