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981.
Comparative metabolic profiling analysis was performed to investigate light- and aeration-dependent regulation of central metabolism in Euglena gracilis. The metabolic profiles of E. gracilis were significantly altered in response to changes in aeration conditions. While many glycolytic intermediates and amino acids accumulated in aerobically grown E. gracilis, a significant reduction in these metabolites was observed for cells under anaerobic conditions, which resulted in elevated production of wax ester. 相似文献
982.
Lechner SG Markworth S Poole K Smith ES Lapatsina L Frahm S May M Pischke S Suzuki M Ibañez-Tallon I Luft FC Jordan J Lewin GR 《Neuron》2011,69(2):332-344
In mammals, the osmolality of the extracellular fluid (ECF) is highly stable despite radical changes in salt/water intake and excretion. Afferent systems are required to detect hypo- or hyperosmotic shifts in the ECF to trigger homeostatic control of osmolality. In humans, a pressor reflex is triggered by simply drinking water which may be mediated by peripheral osmoreceptors. Here, we identified afferent neurons in the thoracic dorsal root ganglia (DRG) of mice that innervate hepatic blood vessels and detect physiological hypo-osmotic shifts in blood osmolality. Hepatic sensory neurons are equipped with an inward current that faithfully transduces graded changes in osmolality within the physiological range (~15 mOsm). In mice lacking the osmotically activated ion channel, TRPV4, hepatic sensory neurons no longer exhibit osmosensitive inward currents and activation of peripheral osmoreceptors in vivo is abolished. We have thus identified a new population of sensory neurons that transduce ongoing changes in hepatic osmolality. 相似文献
983.
Yamashita T Kamata M Endo S Yamamoto M Kakegawa K Watanabe H Miwa K Yamano T Funata M Sakamoto J Tani A Mol CD Zou H Dougan DR Sang B Snell G Fukatsu K 《Bioorganic & medicinal chemistry letters》2011,21(21):6314-6318
The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety. 相似文献
984.
Ushiroda K Maruta K Kitoh M Iwai K Nagamine J Tsuchida A Taiji M Nagata R 《Bioorganic & medicinal chemistry letters》2011,21(1):220-224
Starting with a subtle blood glucose-lowering effect of a TGF-β inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the beneficial effect of 10sNa is attributed to not only its compound PPARα agonistic activity but also its PPARγ partial agonistic activity. 相似文献
985.
986.
Nakajima T Mitsunaga M Bander NH Heston WD Choyke PL Kobayashi H 《Bioconjugate chemistry》2011,22(8):1700-1705
In patients with prostate cancer, a positive surgical margin is associated with an increased risk of cancer recurrence and poorer outcome, yet margin status cannot be determined during the surgery. An in vivo optical imaging probe that could identify the tumor margins during surgery could result in improved outcomes. The design of such a probe focuses on a highly specific targeting moiety and a near-infrared (NIR) fluorophore that is activated only when bound to the tumor. In this study, we successfully synthesized an activatable monoclonal antibody-fluorophore conjugate consisting of a humanized anti-Prostate-Specific Membrane Antigen (PSMA) antibody (J591) linked to an indocyanine green (ICG) derivative. Prior to binding to PSMA and cellular internalization, the conjugate yielded little light; however, after binding an 18-fold activation was observed permitting the specific detection of PSMA+ tumors up to 10 days after injection of a low dose (0.25 mg/kg) of the reagent. This agent demonstrates promise as a method to image the extent of prostate cancer in vivo and could assist with real-time resection of extracapsular extension of tumor and positive lymph nodes. 相似文献
987.
988.
Song Y Funatsu T Tsunoda M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(5-6):335-340
A fast HPLC method using a monolithic silica column was developed for the measurement of amino acids. The amino acids were pre-column derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) and separated on a monolithic silica column (MonoClad C18-HS, 250 mm × 3 mm I.D.). The separation of 19 NBD-amino acids was achieved within 18 min, which was only one-fifth of the time taken by the methods using a conventional particle-packed column, with the gradient elution of a mobile phase at the flow rate of 1.4 mL/min. The sensitivity was good with a limit of detection for the individual amino acids ranging from 2.94 to 53.4 fmol. The calibration curves for all the amino acids were found to be linear in the range of 200 fmol to 20 pmol with correlation coefficients of 0.997 or better. The analytical method was successfully applied to determine the amino acids in a mouse plasma sample. 相似文献
989.
Analytical approaches to poly-γ-glutamate: quantification, molecular size determination, and stereochemistry investigation 总被引:1,自引:0,他引:1
Ashiuchi M 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(29):3096-3101
Poly-γ-glutamate, a nylon-like polyamide material typically consisting of both enantiomers of glutamate, exhibits reasonable biodegradability and its multi-functionality is attracting particular attention. Thus, its industrial application as a versatile and chiral polymer is in increasing demands. Poly-γ-glutamate is presently synthesized using several biocatalysts (e.g., bacterial cells), but the uncontrollable structural diversity of such biosynthesized materials is an area of concern. This review highlights analytical approaches of interest to assure the functional and structural reproducibility of poly-γ-glutamate. 相似文献
990.
Leptin regulates energy balance and glucose homeostasis. Shortly after leptin was identified, it was established that obesity is commonly associated with leptin resistance, though the molecular mechanisms remain to be identified. To explore potential mechanisms of leptin resistance, we employed organotypic brain slices to identify candidate signaling pathways that negatively regulate leptin sensitivity. We found that elevation of adenosine 3', 5'-monophosphate (cAMP) levels impairs multiple signaling cascades activated by leptin within the hypothalamus. Notably, this effect is independent of protein kinase A activation. In contrast, activation of Epac, a cAMP-regulated guanine nucleotide exchange factor for the small G protein Rap1, was sufficient to impair leptin signaling with concomitant induction of SOCS-3 expression. Epac activation also blunted leptin-induced depolarization of hypothalamic POMC neurons. Finally, central infusion of an Epac activator blunted the anorexigenic actions of leptin. Thus, activation of hypothalamic cAMP-Epac pathway is sufficient to induce multiple indices of leptin resistance. 相似文献