SENEX: a CLOS/CLIM application for molecular pathology.
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Amino Acid Sequence↗
Biomedical subjects
V H Mah
Publications and source records attributed to V H Mah.
In situ hybridization of calcium/calmodulin dependent protein kinase II and tau mRNAs; species differences and relative preservation in Alzheimer's disease.
Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression. Calcium/calmodulin dependent protein kinase II (CaM kinase II) has been shown to phosphorylate tau in vitro in such a way to decrease its electrophoretic mobility. A68, apparently a modified form of tau in AD brain, also shows abnormal phosphorylation and slower mobility than tau. To further examine the role of CaM kinase II in AD, in situ hybridization studies were performed on tissues from rat, monkey and human to examine and compare the patterns of CaM kinase II mRNA expression in different brain regions. The most notable differences among the three species were observed in dendrites in layer I of isocortex, in the molecular layer of the dentate gyrus and stratum radiatum and stratum lacunosum-moleculare in hippocampus, where hybridization was detected in rat, but not in monkey or human brain. In addition, comparisons between tau and CaM kinase II mRNA expression were made in tissue from normal aged adults and AD patients, especially in areas prone to NFT formation. CaM kinase II and tau mRNAs were co-expressed in many neuronal populations, both those which are prone to NFT formation as well as those which are rarely affected by AD changes. No major differences in the relative abundance of either CaM kinase II or tau mRNA within particular neuronal populations was noted between normal aged and AD brain. Diminished hybridization was associated with serve neuronal pathology and cell loss.
Aged↗
The SENEX Project: knowledge representation in molecular pathology.
SENEX is a computer program for students, educators, and research investigators in the domain of molecular pathology. The application allows an individual to ask a sequence of questions in a single interactive session, thereby facilitating the development and testing of several hypotheses in a short period of time. Graphical representations of molecules and molecular events help enable individuals to grasp spatial and functional relationships (and in the future, temporal relationships) among molecules, cellular compartments, and cell regions. Fairly simple but well-defined reasoning capabilities allow an individual to ask sophisticated questions and to predict novel molecular events or pathways. SENEX contains information about: 1) molecules and the motifs that impart function to these molecules; 2) molecular events; 3) cell-specific expression of genes; 4) disease processes. SENEX is being developed through object-oriented programming in a portable programming environment supported by COMMON LISP and the COMMON LISP INTERFACE MANAGER.
Data Display↗
SENEX: a computer-based representation of cellular signal transduction processes in the central nervous system.
The SENEX project is exploring knowledge representation in the neurobiology of ageing through object-oriented programming. SENEX is built from a classification structure of biologic entities and significant relationships among them. For example, an enzyme is an entity and an enzymatic reaction is a relationship among enzyme, cofactor(s), substrate(s) and product(s). There are currently 2600 classes of entities and 50 classes of relationships in SENEX. The class structure serves several functions. One function is to interrelate general and specific categories of molecular and morphologic entities. For example, tyrosine kinase and serine/threonine kinase are specific types of the more general class of protein kinase enzymes. Another function of the class structure is to serve as a network through which inheritance of attributes may occur. For example, the attribute 'subunits' is inherited by all subclasses of the general class multisubunit protein. Information may be accessed through links established in the class structure and through links relating one object as part of another. Relationships form the basis of separate modules within SENEX. This paper describes the types of relationships currently used and planned in the representation of age-related changes in cellular signal transduction processes of mammalian central nervous systems. We also describe tools for specific retrieval of relationships and for tracing links in complex reaction cascades. Application of these tools to identifying possible signal transduction pathways to guide further exploration through experimentation is discussed.
Aging↗