No protein is an island.

The yeast two-hybrid (Y2H) system can pump out vast quantities of data on a genome of any size.

has guided cancer research for decades.

Type 1 diabetes, rheumatoid arthritis, and Crohn disease seem clinically diverse, but they arise from acommon problem: poor discrimination between self and nonself.

In the 1960s, researchers found that tricyclic antidepressants (TCAs) alleviated neuropathic pain, such as postherpetic neuralgia.

Acetaminophen poses a pain-relief puzzle.

hler, two researchers at the Medical Research Council's (MRC) Laboratory of Molecular Biology in Cambridge, were investigating the mechanisms underlying the remarkable diversity of antibodies.

In the early years of the 20th century, a new theory, quantum mechanics, revolutionized physicists' understanding of nature.

NO SIGNALING:© 2003 Annual ReviewsAll images redrawn from D. Boehning, S.H. Snyder, Ann Rev Neurosci, 26:105–31, 2003.Neuronal nitric oxide synthase (nNOS) is localized to NMDA receptors by the PDZ-domain adaptor protein PSD95. Calcium entry activates nNOS by a calcium/calmodulin-dependent mechanism. NO can diffuse to neighboring cells to activate soluble guanylyl cyclase or to nitrosylate cysteine residues on target proteins. Nitrosylation inhibits NMDA receptors providing a negative

AGONIZING DIFFERENCES:© 2004 Macmillan Magazines Ltd.(A) GPCR agonists increase the proportion of active receptor states; inverse agonists decrease the proportion of active receptor states; and antagonists inhibit the action of other ligands. (B) In systems with low constitutive receptor activity, inverse agonists will seem to have minimal effect, but might have more effect in a system with high activity. (from Nat Rev Drug Disc, 3:577–626, 2004.)Pharmacologists traditionally divide l

RELEASING THE SECOND MESSENGERS:© 2002 Garland Science/Taylor & Francis BooksIn this common pathway, activated phospholipase C-β hydrolyzes the inositide PI 4,5-bisphosphate to release diacylglyerol and inositol 1,4,5 trisphosphate. IP3 opens specific Ca2+ channels releasing the ions from the lumen of the endoplasmic reticulum. Diacylglycerol can be further cleaved to release arachidonic acid, a signaling molecule needed for the synthesis of other messengers such as prosta-glandins

CALCULATED ESCAPE:Adapted from Y. Iwasa, et al., Proc R soc Lond B Sci, 270: 2573–8, 2003.In this example, genes can mutate at the rate u per gene, per cell division. Gross chromosomal changes occur at the rate p. For this tumor suppressor gene, TSP, Cancer cells have two functioning alleles prior to chemotherapy. Cell reproductive rates Ro-R4 are assumed equal, and a = R/(1-R). Therefore, the critical population size before escape from the therapeutic could happen, N*, can be represented