Molecular orbital differentiation of agonist and antagonist activity in the GlycineB-iGluR-NMDA receptor.

We present various molecular electronic descriptors of agonists and antagonists for Glycine(B)-iGluR-NMDA receptor with a view to identify computational measures that help differentiate between these two classes of biologically active compounds. We use as reference the glycine site in the NR1 subunit of the NMDA receptor (Glycine(B)-iGluR-NMDA). Glycine(B)-iGluR-NMDA receptor is important in learning and memory, and it is involved in various neurodegenerative diseases such as Alzheimer, Parkinson, and Huntington as well as in neuropathies such as schizophrenia and depression. We carried out quantum calculations at two levels, (1) B3LYP Density Functional (6-311G**), and (2) PM3 Hamiltonian for 168 molecules, of which 22 are agonists and 146 are antagonists. Regardless of the quantum mechanical level used we found a consistent signature of agonists versus antagonist action, the energy of the lowest unoccupied molecular orbital (LUMO). Effective differentiation of agonists and antagonists by a single molecular descriptor is seldom seen. We present a plausible electronic structure argument to rationalize these results.

Ionotropic glutamate receptor activated by N-methyl-D-aspartate: a key molecule of conscious life.

We want to propose that basic stereotyped integrative functions are the result of sequentially built neuronal circuits in the primitive regions of the brain in whose build-up a particular subunit composition iGluR-NMDA would play a central role. iGluR-NMDA is a multiregulated heteromeric glutamate receptor-ion channel found in plasma membranes of neurons and other cells. iGluR-NMDA may be composed of up to five subunits, depending on the type of cell involved and its location. There are three major types of subunits and there are variations within each type allowing for up to 13 possible subunits, at least in the rat, which differ from each other in amino acid sequence and thus, in tertiary structure. The actual iGluR-NMDA heteropolymer involved in a given function may thus have a great number of subunit composition possibilities which would be the result of the particular genes expressed in a given type of cell. The iGluR-NMDA is an ion channel that opens in response to glutamate in a highly regulated fashion in which different molecules and ions present in the interstitial fluid determine whether or not the channel opens upon glutamate binding. The original function of iGluR-NMDA may have been that of allowing calcium influx to cells. As the brain receives external stimuli through the senses, new circuits will be formed stepwise in the neocortex in which a particular subunit composition iGluR-NMDA will be involved. Differentiation between external stimuli generated circuits and those governing internal functions will allow distinction between self and non-self, thus generating conscious awareness. The role of the particular subunit composition iGluR-NMDA proposed would be that of providing a means of calcium influx to the synapses to be formed and, if the same stimulus is forthcoming, allowing permanent synapses formation through the membrane incorporation of calcium dependent adhesion molecules such as cadherins and cytoskeleton reorganization promoted by nectins.

From food basket to food security. The food factor in nutritional surveillance.

One important indicator of nutritional surveillance is the one devoted to monitor food security. The experience toward the development of one of such indicators is presented. This includes the development of a food basket, defined as the group of foods that meet the characteristics such as is now consumed by important population segments of the community; it contributes a substantial portion of the calories and proteins purchased, and is responsible for an important proportion of the food budget. The concept implies a dynamic food basket, the quantities of which are calculated in a way that simulates the behavior of the consumer and the best nutrition knowledge. For this purpose we use linear program techniques. A measure of the risk of being unable to buy the foods needed for a family is presented, and is used as a proxy for food security risk. In the appendix, the mathematical expressions of the model used for a linear program is also presented.

From food basket to food security. The food factor in nutritional surveillance

One important indicator of nutritional surveillance is the one devoted to monitor food security. The experience toward the development of one of such indicators is presented. This includes the development of a food basket, defined as the group of foods that meet the characteristics such as is now consumed by important population segments of the community; it contributes a substantial portion of the calories and proteins purchased, and is responsible for an important proportion of the food budget. The concept implies a dynamic food basket, the quantities of which are calculated in a way that simultates the behavior of the consumer and the best nutrition knowledge. For this purpose we use linear program techniques. A measure of the risk of being unable to buy the foods needed for a family is presented, and is used as a proxy for food security risk. In the appendix, the mathematical expressions of the model used for a linear program is also presented