Faculty Bibliography

The total synthesis of (-)-frondosin B, the enantiomer of naturally-occuring (+)-frondosin B, is described, wherein a palladium-catalyzed cyclization is used to establish the tetracyclic ring system of the natural product. (C) 2004 Elsevier Ltd. All rights reserved.

Neurotrophins play many critical roles in regulating neuronal plasticity, survival, and differentiation in the nervous system. Neurotrophins recognize two different receptors, the Trk receptor tyrosine kinase and the p75 neurotrophin receptor, which are associated closely. Several adaptor proteins are associated with each receptor. An ankyrin-rich membrane spanning protein (ARMS), originally identified as a substrate for protein kinase D (Kidins220) and as a p75 interacting protein, serves as a novel downstream target of Trk receptor tyrosine kinases. Kidins220/ARMS is co-expressed frequently with Trk and p75 and represents the only membrane-associated protein known to interact with both receptors. We report here that a ternary complex can be formed between Trk, p75, and Kidins220/ARMS. The extracellular domains of the TrkA and the p75 receptors are necessary for their association, whereas the juxtamembrane region of p75 was responsible for the interaction with Kidins220/ARMS. Interestingly, increasing the level of Kidins220/ARMS expression resulted in a decreased association of TrkA with p75. These findings thus suggest that Kidins220/ARMS plays an important role in regulating interactions between Trk and p75 neurotrophin receptors

Increased iron store in the body may increase the risk of many diseases such as cancer and inflammation. However, the precise pathogenic mechanism of iron has not yet been elucidated. In the present study, the early biological responses of cells to iron treatment were investigated in AP-1 luciferase reporter stably transfected mouse epidermal JB6 cells and primary rat hepatocytes. It was shown that water-soluble iron compounds, such as FeSO4 and Fe2(SO4)3, were more active in inducing AP-1 in JB6 cells than water-insoluble iron compounds, such as Fe2O3 and FeS. Iron stimulated mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-jun NH2 terminal kinases (JNKs), both in JB6 cells and in primary rat hepatocytes, as determined by the phosphorylation assay. Interestingly, the increase in AP-1 luciferase activity by iron was inhibited by the pretreatment of the cells with PD98059, a specific MEK1 inhibitor, and SB202190, a p38 kinase inhibitor. Levels of interleukin-6 (IL-6), a pro-inflammatory cytokine, were increased in JB6 cells by iron in a dose-dependent manner. The increase in IL-6 and its mRNA by iron was also eliminated by the pretreatment of the cells with PD98059 and SB202190. Since the IL-6 promoter contains an AP-1 binding site, our studies indicate that the iron-induced IL-6 gene expression may be mediated through ERKs and p38 MAPK pathways, possibly one of the important mechanisms for the pathogenesis of iron overload

Economics, psychology, and neuroscience are converging today into a single, unified discipline with the ultimate aim of providing a single, general theory of human behavior. This is the emerging field of neuroeconomics in which consilience, the accordance of two or more inductions drawn from different groups of phenomena, seems to be operating. Economists and psychologists are providing rich conceptual tools for understanding and modeling behavior, while neurobiologists provide tools for the study of mechanism. The goal of this discipline is thus to understand the processes that connect sensation and action by revealing the neurobiological mechanisms by which decisions are made. This review describes recent developments in neuroeconomics from both behavioral and biological perspectives.

Studies in heterologous systems have demonstrated that heterodimerisation of the two GABA(B) receptor subunits appears to be crucial for the trafficking and signalling of the receptor. Gene targeting of the GABA(B1) gene has demonstrated that the expression of GABA(B1) is essential for GABA(B) receptor function in the central nervous system (CNS). However, the contribution of the GABA(B2) subunit in the formation of native GABA(B) receptors is still unclear, in particular whether other proteins can substitute for this subunit. We have created a transgenic mouse in which the endogenous GABA(B2) gene has been mutated in order to express a C-terminally truncated version of the protein. As a result, the GABA(B1) subunit does not reach the cell surface and concomitantly both pre- and post-synaptic GABA(B) receptor functions are abolished. Taken together with previous gene deletion studies for the GABA(B1) subunit, this suggests that classical GABA(B) function in the brain is exclusively mediated by GABA(B1/2) heteromers

Computed Tomography (CT) is one of the most sensitive medical imaging modalities for detecting pulmonary nodules. Its high contrast resolution allows the detection of small nodules and thus lung cancer at a very early stage. In this paper, we propose a method for automating nodule detection from high-resolution chest CT images. Our method focuses on the detection of discrete types of granulomatous nodules less than 5 mm in size using a series of 3D filters, Pulmonary nodules can be anywhere inside the lung, e.g., on lung walls near vessels, or they may even be penetrated by vessels,. For this reason,, we first develop a new cylinder filter to suppress vessels, and noise. Although nodules usually have higher intensity values than surrounding regions, many malignant nodules are of low contrast. In order not to ignore low contrast nodules, we develop a spherical filter to, further enhance nodule intensity values, which is a novel 3D extension of Variable N-Quoit filter. As with most automatic nodule detection methods, our method generates false positive nodules. To address this, we also develop a filter for false positive elimination. Finally, we present promising results of applying our method to various clinical chest CT datasets with over 90% detection rate