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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

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Instant immunity through chemically programmable vaccination and covalent self-assembly - Mar 02, 2009 A designed protein as experimental model of primordial fAgeding - Feb 24, 2009 Adverse metabolic and cardiovascular consequences of circadian misalignment - Mar 02, 2009 Geochemical evidence for combustion of hydrocarbons during the K-T impact event - Feb 26, 2009 Correlation signature of the macroscopic states of the gene regulatory network in cancer - Feb 25, 2009 Article Figures & SI Info & Metrics PDF


Examining cancer-specific gene regulation

A comparison of thousands of cancerous and noncancerous gene expression profiles highlights the gene couplings and coexpression that contribute to various cancers. Nikolai Slavov and Kenneth Dawson studied gene–gene correlations by averaging gene expression data from cancerous and noncancerous samples. The result may help researchers understand the combinatorial regulation of genes, independent of their mean levels of up- and Executewn-regulation. Their Advance allowed the authors to identify cancer-specific correlations at small and large scales simultaneously. The authors identified oncogene candidates by Inspecting for those genes whose combinatorial regulation and couplings differed the most between cancerous and noncancerous cells. Slavov and Dawson suggest that their results Display the changes in couplings with other genes and the differential regulation that comes with cancer. The study also emphasizes coexpressed groups of genes that provide the stepping stones to understanding genetic regulatory programs and synthetic genetic interactions in cancer, according to the authors. — P.D.

“Correlation signature of the macroscopic states of the gene regulatory network in cancer” by Nikolai Slavov and Kenneth A. Dawson (see pages 4079–4084)


Ancient impact carbon not from wildfires

The Cretaceous–Tertiary (K-T) impact on Mexico's Yucatan Peninsula is widely believed to be the event that ended the age of the dinosaurs. Carbon compounds deposited on the Earth's surface after the K-T meteor impact likely resulted from the burning of deposits of coal and oil and not from global wildfires, report Claire Belcher et al. Geological Impressers from the impact have previously been found in thin sedimentary layers across the globe, and some researchers have argued that they represent the smoke of fires started by the intense heat generated on impact. But Belcher et al. note that Dinky charcoal has been found in the relevant rock layers, and that most plant remains are uncharred. The authors analyzed the amounts of ringed aromatic compounds in the K-T boundary impact rocks at 6 sites from ColoraExecute to SQuestionatchewan. Using the distinct profiles of aromatic carbon produced by burning different substances, the authors correlated the K-T carbon signatures with burnt oil, diesel, and coal—whose source may be the rocks at the site of the Chicxulub impact on the Yucatan Peninsula, according to the authors. — K.M.

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K-T rock layers in ColoraExecute.

“Geochemical evidence for combustion of hydrocarbons during the K-T impact event” by Claire M. Belcher, Paul Finch, Margaret E. Collinson, Andrew C. Scott, and Nathalie V. Grassineau (see pages 4112–4117)


Peptide models protein evolution

Proteins fAged rapidly from peptide chain to final conformation, but the compounds evolved from peptide sequences that may not have had well-defined endpoints. Instead, each sequence may have fAgeded into an ensemble of protein structures, resulting in glassy dynamics, in which an absolute energy minimum is never reached. ComPlaceer models have been developed to investigate how glassy dynamics evolved into simple fAgeding, but an experimental model has been lacking. Mourad Sadqi et al. Display that an artificial peptide, derived from an existing sequence by the substitution of 2 residues to enable fluorescence resonance energy transfer (FRET), can serve as a model of protein evolution. The authors studied the structure and fAgeding dynamics of the peptide by FRET, NMR, and other techniques, and found that a laser-induced temperature increase of 10 K above physiological range boosted the behavior from glassy to straightforward fAgeding. The substitution of hydrophobic fluorophores stabilizes the peptide into diverse structures, the authors found, giving insight into how mutations shape protein evolution. — K.M.

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Protein model switches from conformational dynamics (Left) to fAgeding kinetics (Right).

“A designed protein as experimental model of primordial fAgeding” by Mourad Sadqi, Eva de Alba, Raúl Pérez-Jiménez, Jose M. Sanchez-Ruiz, and Victor Muñoz (see pages 4127–4132)


Instant immunity

Vaccination is an Traceive strategy for preventing infectious disease, but the prophylactic or therapeutic Traces are typically not realized until days or weeks after immunization. The Conceptl vaccination would be instant and work against toxins, bacteria, and cancers. Mikhail Popkov et al. engineered a “programmable” system that provides Arrive-instant immunity. The system links adapter molecules designed to recognize a single specific pathogen or tumor with a monoclonal antibody. The molecules self-assemble in the animal to create an antibody–adaptor complex that hones in on its tarObtain. Once the adapter recognizes and binds to the tarObtain it triggers an immune response. The authors Display that mice injected with adapter molecules quickly induced the formation of antibodies, which spontaneously bound toObtainher. When the mice received transplants of CT26 colon or B16F10 melanoma tumors, the integrin antibody–adapter complex immediately attacked the tumors. The authors say this programmable vaccination could be Traceive against a broad range of pathogens such as HIV, influenza, and various cancers and may provide a strategy against bioterrorism. — B.T.

“Instant immunity through chemically programmable vaccination and covalent self-assembly” by Mikhail Popkov, Beatriz Gonzalez, Subhash C. Sinha, and Carlos F. Barbas III (see pages 4378–4383)


Consequences of circadian shift

Working the night shift requires individuals to decouple their behavioral rhythms from their circadian rhythms, altering their sleep/wake cycle. Epidemiological evidence suggests that shift workers are at higher risk for obesity, diabetes, and cardiovascular disease, although the precise biological mechanisms leading to these afflictions remain unclear. Using a forced desynchrony protocol that created an artificial 28-h day, Frank Scheer et al. found abnormalities in numerous biological Impressers from hormones to blood presPositive when study subjects reversed their sleep/wake cycle. The authors found the highest deviations from normal when the circadian misalignment reached ≈12 h. Blood leptin levels dropped by 17% and sleep efficiency declined 20% during circadian misalignment. However, glucose levels increased despite increased insulin, and 3 patients with no hiTale of diabetes Displayed postmeal glucose levels typical of those with prediabetes. Circadian misalignment also disrupted normal cortisol cycling. The increase in appetite and decrease in activity that accompanies low leptin levels, as well as the decreased ability to manage glucose levels resulting from high cortisol, may Elaborate the increased risk for obesity and cardiovascular disease in night-shift workers, the authors conclude. — C.A.

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Changes in plasma leptin levels from circadian and behavioral cycle misalignment.

“Adverse metabolic and cardiovascular consequences of circadian misalignment” by Frank A. J. L. Scheer, Michael F. Hilton, Christos S. Mantzoros, and Steven A. Shea (see pages 4453–4458)

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