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Pharmacogenomics Lurches Forward

By | August 2, 2004

PREDICTIVE POWER:© 2004 Massachusetts Medical SocietyThis analysis of gene expression ranks 36 genes on the basis of their predictive power (univariate z score), with a negative score associated with longer overall survival and a positive score associated with shorter overall survival. The dashed lines represent an absolute univariate z score of ± 1.5. The prediction model is based on the weighted expression of six genes in the equation shown. (N Engl J Med, 350:1828–37, 2004.)Me

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Receptor Redemption

By | August 2, 2004

A MUTANT MAP:Courtesy of Michael ConnAbove are the loci for all known naturally occurring mutants of the human gonadotropin releasing hormone receptor (GnRHR) identified from patients with hypogonadotropic hypogonadism (HH). The vast majority of point mutations can be functionally rescued through the use of a pharmacological chaperone. Some others had not been attempted. Twelve mutations identified in yellow letters result in modest charge changes. A smaller number result in other changes to the

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Crossing the Frontlines in Mucosal Immunity

By | July 19, 2004

WORKING IN CONCERT:Courtesy Katherine L. Knight and Ki-Jong Rhee © 2004 American Association of ImmunologistsLeft is a section of appendix following introduction of Bacteroides fragilis; right is a section of appendix following introduction of B. fragilis plus Bacillus Subtilis. B. fragilis alone results in no gut-associated lymphoid tissue (GALT) development while the combination shows a B lymphocyte follicle (red dots).Commensal or nonpathogenic bacteria have established a mutually benefi

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Magicicada

By | July 19, 2004

Tammy Irvine, http://www.rearviewstudio.comBig, loud, and astonishingly clumsy, periodical cicadas dally underground for nearly their entire long lives (17 or sometimes 13 years) and then emerge all at once by the millions, in May, when the soil has warmed to the mid-60s. The males form choruses in the trees, belting out love songs loud enough to damage human hearing. Each female selects just one troubadour, mates, and lays her eggs in twigs; then all the adults die. The process takes only three

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Meiosis Models Face Tough Scrutiny

By | July 19, 2004

A TALE OF TWO MODELS:Courtesy of Douglas K. Bishop and Denise Zickler, © Elsevier ScienceThe double-strand-break repair model (A) posits that during meiotic prophase I, crossovers (COs) and noncrossovers (NCOs) begin with a double-strand break (DSB) of a DNA helix. Cleavage of a structure known as the Holliday junction (HJ) ultimately generates both COs and NCOs. A newer model (B) proposes that COs still arise from HJs (right) but that NCOs come from a pathway called synthesis-dependent str

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Tracking the Red-Eyed, Sluggish, and Ear-Splitting

By | July 19, 2004

© Chris Simon, University of ConnecticutTwo cicadas mate.It's a bit tricky, getting a tiny drop of Super Glue in exactly the right place on a cicada's thorax. Martin Wikelski must affix his microtransmitter far enough forward so that it doesn't interfere with her wings, because her wings, and how far she flies with them, are why Wikelski, a physiological ecologist at Princeton University, is spending a cloudy May morning watching ungainly red-eyed insects struggle out of their exoskeletons

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Building Meaningful Climate Models

By | July 5, 2004

Climate-change predictions are fraught with uncertainty. To build meaningful models of temperature and sea-level changes throughout the 21st century, researchers contributing to the Intergovernmental Panel on Climate Change's (IPCC) Third Assessment Report produced a set of four storylines that qualitatively assess social, economic, cultural, and political climes throughout the 21st century. These are developed into quantitative greenhouse-gas emission models called the Special Report on Emissio

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Iron Seeding Just Doesn't Pay

By | July 5, 2004

BRINGING ON THE NEXT ICE AGE?Dee Breger, Drexel UniversityAssumptions that tiny diatoms such as the ones shown above could fix carbon from the air and sink it to the bottom of the ocean have been hard to prove.The US Department of Energy has taken an interest in carbon sequestration, but a grand scheme to induce thick blooms of carbon-fixing algae has yet to bear fruit in early studies. The DOE directs a large share of its global warming budget to carbon-sequestration research, drawing on biolog

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Scratching the Surface for Estrogen's Effects

By | July 5, 2004

A BUSY HORMONE:© 2001 Annual ReviewsEstrogen's direct genomic effects are mediated by the nuclear form of the estrogen receptors ERα or ERβ which associate with the Estrogen Response Element (ERE) or the fos/jun heterodimers that bind AP1 sites. Indirect genomic mechanisms include activation of ER-linked second messenger systems such as AC/PKC, cAMP/PKA and MAPK/ERK. Ras activates Raf, leading to sequential phosphorylation and activation of MAPK/ERK which interacts directly with n

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Computing Gene Regulation

By | June 21, 2004

TRANSCRIPTIONAL DIVERSITY:Horst Feldmann, Ludwig-Maximilians-Universität MüchenTranscription by Pol II is dependent on a number of multi-subunit complexes including TFIID, a general transcription factor complex, and SAGA. Both deliver the TATA-box binding protein (TBP) to promoters and they share a number of TBP associated factors (TAFs). While they have overlapping contributions to gene expression, TFIID function appears to dominate gene regulation at 90% of the measurable genome, mos

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