A Web Services architecture for UMLS Knowledge Sources.

A web service is a collection of industry standards to enable reusability of services and interoperability of heterogeneous applications. The UMLS Knowledge Source (UMLSKS) Server provides remote access to the UMLSKS and related resources. We propose a Web Services Architecture that encapsulates UMLSKS-API and makes it available in distributed and heterogeneous environments. This is the first step towards intelligent and automatic UMLS services discovery and invocation by computer systems in distributed environments such as web.

PREDICTION OF DNA METHYLATION BASED ON GENOMIC ARCHITECTURE AND APPLICATIONS OF POSITIONAL WEIGHT MATRICES

Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible loss of gene function. In our genome wide analysis of human genes, results suggested that 22% of the genes in cancer were predicted to be methylation-prone; in cancer these genes are generally down-regulated and function in the development process. In summary, our investigation validated our hypothesis and showed that these widespread genomic elements in cancer are highly associated with promoter DNA methylation and may further participate in influencing epigenetic regulation.

Functional architecture of mammalian horizontal cells

In the rabbit retina, there are two kinds of horizontal cells (HCs). The A-type HC is a large axonless cell which contacts cones exclusively. The B-type HC is an axon bearing cell. While the somatic dendrites of B-type HCs also contact cones, the axon expands into an elaborately branched structure, the axon terminal (AT), which contacts a large number of rods. It is difficult to label the different HCs selectively by immunochemical methods. Therefore, we developed dye injection methods to label each type of HC. Then it was possible, (1) to describe the detailed structure of the AT (2) to identify the glutamate receptors mediating cone input to A and B-type HCs and rod input to ATs and (3) to test the hypothesis that the B-type HCs are coupled via Cx57 gap junctions. ^ To obtain well filled examples of single HCs, it was necessary to block gap junction coupling to stop the spread of Neurobiotin through the network. We used dye coupling in A-type HCs to screen a series of potential gap junction antagonists. One of these compounds, meclofenamic acid (MFA), was potent, water soluble and easily reversible. This compound may be a useful tool to manipulate gap junction coupling. ^ In the presence of MFA, Neurobiotin passed down the axon of B-type HCs to reveal the detailed structure of the AT. We observed that only one AT ending entered each rod spherule invagination. This observation was confirmed by calculation and two dye injections. ^ Glutamate is the neurotransmitter used by both rods and cones. AMPA receptors were colocalized with the dendrites of A and B-type HCs at each cone pedicle. In addition, AMPA receptors were located on the AT ending at each rod spherule. Thus rod and cone input to HCs is mediated by AMPA receptors. ^ A-type and B-type HCs may express different connexins because they have different dye-coupling properties. Recently, we found that connexin50 (Cx50) is expressed by A-type HCs. B-type HCs and B-type ATs are also independently coupled. Cx57 was expressed in the OPL and double label studies showed that Cx 57 was colocalized with the AT matrix but not with the somatic dendrites of B-type HCs. ^ In summary, we have identified a useful gap junction antagonist, MFA. There is one AT ending at each rod spherule, rods inputs to ATs is mediated by AMPA receptors and coupling in the AT matrix is mediated by Cx57. This confirms that HCs with different properties use distinct connexins. The properties of ATs described in this research are consistent. The connections and properties reported here suggest that ATs functions as rod HCs and provide a negative feedback signal to rods. ^