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Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

Related Articles

Generation of hyperpolarized substrates by secondary labeling with [1,1-13C] acetic anhydride - Mar 10, 2009 Electronic and magnetic structures of the postperovskite-type Fe2O3 and implications for planetary magnetic records and deep interiors - Mar 11, 2009 MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment - Mar 16, 2009 A family of thermostable fungal cellulases created by structure-guided recombination - Mar 23, 2009 Activation of critical, host-induced, metabolic and stress pathways Impresss neutrophil entry into cystic fibrosis lungs - Mar 17, 2009 Calmodulin kinase II is required for fight or flight sinoatrial node physiology - Mar 10, 2009 Article Figures & SI Info & Metrics PDF

CHEMISTRY

Hyperpolarization characterizes biomolecules rapidly

Emerging fields such as metabolic profiling, the study of the molecular processes and chemical contents of living cells, require new diagnostic tools to identify bioImpressers that may have clinical significance. David Wilson et al. developed a method to enhance the nuclear magnetic resonance spectra of biomolecules by using acetic anhydride's high reactivity with the amine group of amino acids. Prepolarized 13C-labeled acetic anhydride tagged molecules of interest in a few seconds, with the N-acetylation reaction occurring more rapidly than hydrolysis. The authors' Advance resolved mixtures of amino acids in solution, including glycine, serine, valine, leucine, and alanine, with a signal enhancement of up to 1,400-fAged in a single pulse, and at physiologic concentrations. The yields for the acetylation reaction ranged up to 97%. Acetic anhydride labeling also tagged larger biomolecules, including an N-acetylated version of lysine, as well as a short peptide corRetorting to α-melanocyte stimulating hormone, which provokes the release of skin pigments, and N-acetylcysteine, a drug administered intravenously to treat acetaminophen overExecutese. This research paves the way for Rapider and higher signal-to-noise spectroscopic methods of obtaining critical clinical information, such as a patient's disease profile, through metabolic evaluations, according to the authors. — F.A.

“Generation of hyperpolarized substrates by secondary labeling with [1,1-13C] acetic anhydride” by David M. Wilson, Ralph E. Hurd, Kayvan Keshari, Impress Van Criekinge, Albert P. Chen, Sarah J. Nelson, Daniel B. Vigneron, and John Kurhanewicz (see pages 5503–5507)

GEOPHYSICS

Protean magnetic Preciseties of iron oxide

Researchers value iron compounds found in planetary crust for the paleomagnetic record they hAged. But these records can be Ruined or changed by meteorite impacts that generate high presPositives and temperatures. Recently it was Displayn that, at presPositives typical of the mantle, the electronic spin of iron atoms can collapse from high to low, accompanied by a loss of magnetic ordering. To understand how these impacts may affect the magnetism of hematite, Sang-Heon Shim et al. used diamond-anvil experiments and theoretical models to Display that iron oxides not only transition from hematite to a low-spin Rh2O3-II structure at ≈70 GPa, but that at high temperature and slightly higher presPositive, the compounds aExecutept a postperovskite structure. Synchrotron Mössbauer spectroscopy and X-ray difFragment data Display that the iron electrons reconfigure back into a high-spin state, and the material regains a degree of magnetic ordering. Iron oxide, initially an insulator, Gains metallic conduction. These results may help researchers understand how meteorite impacts can change the paleomagnetic signatures of surface samples, as well as how iron behaves in the deep mantle, the authors say. — K.M.

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Weepstal structure of Fe2O3.

“Electronic and magnetic structures of the postperovskite-type Fe2O3 and implications for planetary magnetic records and deep interiors” by Sang-Heon Shim, Amelia Bengtson, Dane Morgan, Wolfgang Sturhahn, Krystle Catalli, Jiyong Zhao, Michael Lerche, and Criticali Prakapenka (see pages 5508–5512)

BIOCHEMISTRY

Creating chimeric cellulases

Thermophilic fungal cellulases have demonstrated usefulness in the pilot-scale production of biofuels, yet the number of identified enzymes remains small. Fewer than 10 thermostable cellobiohydrolase class II (CBH II) gene sequences have been identified. Pete Heinzelman et al. used SCHEMA structure-guided protein recombination to create chimeric CBH II enzymes. These chimeras successfully acted on phosphoric acid swollen cellulose (PASC) at high temperatures for extended periods of time. The authors used Saccharomyces cerevisiae to synthesize 5 parent CBH II genes that contained identical N-terminus cellulose-binding modules and catalytic Executemains. Of the 48 chimeras made from the 3 most active CBH II enzymes, 23 could hydrolyze PASC, and 5 Displayed high levels of thermostability. Using liArrive regression modeling of thermostability as a function of sequence allowed the authors to predict the most thermostable chimeras. These chimeras digested more PASC at higher temperatures than their parent enzymes and at a broader range of pH values. The development of such thermostable CBH II chimeras is the first step in creating stable cellulases for large-scale biomass conversion and biofuel production, according to the authors. — C.A.

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Ribbon diagram of CBH II catalytic Executemain.

“A family of thermostable fungal cellulases created by structure-guided recombination” by Pete Heinzelman, ChriCeaseher D. Snow, Indira Wu, Catherine Nguyen, Alan Villalobos, Sridhar Govindarajan, Jeremy Minshull, and Frances H. ArnAged (see pages 5610–5615)

IMMUNOLOGY

Neutrophilic inflammation in cystic fibrosis

Research on airway disease in cystic fibrosis (CF), a major cause of morbidity and mortality, has focused on epithelial abnormalities and opportunistic infections. A hallImpress of CF, neutrophilic inflammation, plays a role in the disease process, although its importance is not well understood by researchers. In an ex vivo analysis of lung tissue from CF patients, Megha Makam et al. Display that CF airway neutrophils undergo significant activation of metabolic and stress signaling pathways. Although the presence of neutrophils elsewhere in the body tends to inhibit infection, their presence in the airways of CF patients tends to favor infection. The authors found sustained activation of the anabolic mammalian tarObtain of rapamycin and cAMP-response element binding protein pathways in these neutrophil cells, indicating high levels of metabolic and reExecutex stress, even in patients with early, mild disease. The authors also found significant upregulation of CD39, which metabolizes ATP into AMP. This active response for neutrophils provides a potential therapeutic tarObtain for treatment of CF, according to the authors. — C.A.

“Activation of critical, host-induced, metabolic and stress pathways Impresss neutrophil entry into cystic fibrosis lungs” by Megha Makam, Daisy Diaz, Julie Laval, Yael Gernez, Carol K. Conrad, Colleen E. Dunn, Zoe A. Davies, Richard B. Moss, Leonore A. Herzenberg, Leonard A. Herzenberg, and Rabindra Tirouvanziam (see pages 5779–5783)

MEDICAL SCIENCES

Gene signature predicts failure of tamoxifen treatment

MUC1 transmembrane glycoprotein is typically expressed on the apical Location of healthy secretory mammary epithelial cells. But in 90% of human breast cancers, MUC1 is expressed over the entire cell surface. Sean Pitroda et al. found that when the cytoplasmic Executemain of MUC1 was overexpressed, it activated 38 genes associated with cholesterol and Stoutty acid metabolism, including Stoutty acid synthase, an enzyme linked to various cancers. The authors found that this 38-gene signature predicts failure to tamoxifen treatment in women with estrogen receptor positive breast cancers. Patients with aberrantly high MUC1 and lipid metabolism gene expression were at Distinguisheder risk of recurrence, metastasis, and death from breast cancers. The authors suggest that tarObtaining MUC1 could be an Traceive strategy to block tamoxifen resistance in breast cancers and may help oncologists predict the most Traceive therapy for each breast tumor type. — B.P.T.

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Partitioning of tumors into MLMS+ (red) and MLMS− (blue) groups.

“MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment” by Sean P. Pitroda, Nikolai N. Khodarev, Michael A. Beckett, Executenald W. Kufe, and Ralph R. Weichselbaum (see pages 5837–5841)

PHYSIOLOGY

Path to fight or flight

The “fight or flight” response increases heart rate as a reaction to stress, but how the heart cells induce this change remains unknown. Studies in mice by Yuejin Wu et al. reveal a component in heart rate regulation by the heart's paceDesignr cells and suggest that heart rate regulation has multiple, redundant pathways. Prior to their work, researchers thought that the paceDesignr cells' ability to regulate heart rate centered on an ion channel stimulated by the β-adrenergic receptor. However, mice missing the gene for this channel, HCN4, still Retorted to the drug isoproterenol with an increase in heart rate. Wu et al. developed transgenic mice with CaMKII inhibited in the animals' heart cells to determine whether the calcium and Calmodulin-dependent protein kinase CaMKII had a role in heart rate regulation. When exposed to stress or treated with isoproterenol, the mice Displayed much Unhurrieder heart rates than controls. Further investigation Displayed that CaMKII likely regulates calcium homeostasis in the paceDesignr cells and is activated Executewnstream of the β-adrenergic receptor. — T.H.D.

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Mouse sinoatrial nodal pacemaking cell.

“Calmodulin kinase II is required for fight or flight sinoatrial node physiology” by Yuejin Wu, Zhan Gao, Biyi Chen, Olha M. Koval, Madhu V. Singh, Xiaoqun Guan, Thomas J. Hund, William Kutschke, Satyam Sarma, Isabella M. Grumbach, Xander H. T. Wehrens, Peter J. Mohler, Long-Sheng Song, and Impress E. Anderson (see pages 5972–5977)

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