In this issue

Abstract The proteome of an innate small molecule drug pp. 23–37 Isatin is an interesting molecule in its own right ‐ endogenous, it is delivered in a discrete pattern to specific organs, including the brain. It is also the starting material for synthesis of a diverse set of pharmaceuticals and pesticides. What are the targets of this multi‐talented molecule? Buneeva et al . tackled the question with proteomic tools, including affinity chromatography and SELDI, and demonstrated the utility of a validated optical biosensor (Biacore 3000) for studies of molecular affinities. One interesting observation was that although mouse and rat brain gave 65 and 64 individual proteins respectively, only one‐third of them matched ‐ an unusual result for so closely related species. It may be explained in part by species differences in affinity for the chromatography matrices, aminocaproyl‐ and 5‐amino‐isatin.Type II diabetes agents line up against β cells pp. 59–71 Insulin is roduced by pancreatic β cells normally under tight control. Failure of that regulation can ead to type II diabetes. Hence, what causes loss of control? One factor is chronic hyperglycemia, which is toxic to β cells. Couté et al . looked further into the matter after checking their weapons: INS‐1E ‐ an insulin secreting cell line, stable isotope labeling by amino acids in cell culture (SILAC), apoptosis detectors, insulin detectors, gene arrays, a MALDI TOF/TOF mass spectrometry, etc. To see what hyperglycemia attacked first, short pulses of SILAC were analyzed for proteins showing shifts in abundance. The most striking changes were in the proteins involved in lipid transport and metabolism: epidermal fatty acid binding protein, cellular retinoic acid binding protein 1, and fatty acid synthetase. Corresponding mRNAs were also upregulated. Lipogenesis effects on insulin synthesis were found within 24h of perturbation.Hazardous hors d'oeuvres/entrees/starters pp. 81–89 Although it has never been certified by reliable witnesses, the cannibalistic transmission of Creutzfeld‐Jakob disease (CJD) makes a good story. A human prion disease, CJD is similar to bovine spongiform encephalitis (BSE, mad cow disease), which is spread by the practice of feeding cattle the remains of sick cattle, including brain and spinal nerve cord. The neurodegenerative disease is difficult to diagnose in humans except by neuropathological examination. Steinacker et al . extended their previous work on 2‐D DIGE CSF screening to SELDI‐TOF, which has a more appropriate mass range and is much faster. Evaluating CJD cases and other dementias and non‐dementia cases as controls, they found a potential new marker: ubiquitin, 8608Da. Additional immunoreagents are required for full validation of the marker.