Type 2 diabetes progression: A regulatory network approach.

In order to elucidate central elements underlying type 2 diabetes, we constructed a regulatory network model involving 37 components (molecules, receptors, processes, etc.) associated to signaling pathways of pancreatic beta-cells. In a first approximation, the network topology was described by Boolean rules whose interacting dynamics predicted stationary patterns broadly classified as health, metabolic syndrome, and diabetes stages. A subsequent approximation based on a continuous logic analysis allowed us to characterize the progression of the disease as transitions between these states associated to alterations of cell homeostasis due to exhaustion or exacerbation of specific regulatory signals. The method allowed the identification of key transcription factors involved in metabolic stress as essential for the progression of the disease. Integration of the present analysis with existent mathematical models designed to yield accurate account of experimental data in human or animal essays leads to reliable predictions for beta-cell mass, insulinemia, glycemia, and glycosylated hemoglobin in diabetic fatty rats.

Translocation properties of primitive molecular machines and their relevance to the structure of the genetic code.

We address the question, related with the origin of the genetic code, of why are there three bases per codon in the translation to protein process. As a follow-up to our previous work (Aldana et al., 1998, Martínez-Mekler et al., 1999a,b), we approach this problem by considering the translocation properties of primitive molecular machines, which capture basic features of ribosomal/messenger RNA interactions, while operating under prebiotic conditions. Our model consists of a short one-dimensional chain of charged particles (rRNA antecedent) interacting with a polymer (mRNA antecedent) via electrostatic forces. The chain is subject to external forcing that causes it to move along the polymer which is fixed in a quasi-one-dimensional geometry. Our numerical and analytic studies of statistical properties of random chain/polymer potentials suggest that, under very general conditions, a dynamics is attained in which the chain moves along the polymer in steps of three monomers. By adjusting the model in order to consider present-day genetic sequences, we show that the above property is enhanced for coding regions. Intergenic sequences display a behavior closer to the random situation. We argue that this dynamical property could be one of the underlying causes for the three-base codon structure of the genetic code

Primitive molecular machine scenario for the origin of the three base codon composition.

We set up a scenario for the operation of primordial synthesis machines operating in outer space quasi one dimensional channels, where polymers interact with fixed particles. The scheme allows for polymerization, translocation and translation. We will show that under very general conditions the particle/polymer interaction potential has spatial regularities with an average distance of three between neighboring minima. We present a model that exhibits how primitive molecular machines may convert the structural properties of the potential into locomotion regularities. On average, polymer movement takes place by shifts with long time intervals every three displacements. We argue that this feature is generic and lies at the origin of the three base codon composition.

Antigenic homology of HIV-1 GP41 and human platelet glycoprotein GPIIIa (integrin beta3).

Fifty-eight of 89 serum samples (65.17%) from HIV-1-infected individuals at various disease stages contain antibodies that react with a platelet peptide located in the cytoplasmic domain of integrin beta3, glycoprotein GPIIIa (aa749-761; sequence DRKEFAKFEEERA). Rabbit polyclonal antibodies raised against the synthetic platelet peptide also react with the structurally homologous HIV-1 gp41-derived peptide (EKNEQELLELDKW(A)) and bind to a Western blot band with molecular weight corresponding to HIV-1 gp41. These findings point to molecular mimicry between HIV-1 and a human membrane protein found in platelets and other cells that could be of pathologic consequence.

Structural and thermodynamic properties of DNA uncover different evolutionary histories.

We propose an index of DNA homogeneity (IDH) based on a binary distribution model that quantifies structural and thermodynamic aggregates present in DNA primary structures. Extensive analysis of sequence databases with the IDH uncovers significant constraints on DNA sequence other than those derived from codon usage or protein function. This index clearly distinguishes between organisms of different evolutive origins and places them in disjoint domains of DNA sequence space.

Discrete systems, cell-cell interactions and color pattern of animals. I. Conflicting dynamics and pattern formation.

The morphogenesis of the color pattern of animals is modeled within the framework of a clonal model. The model takes into account the, sometimes conflicting, cell-cell and cell-background interactions. The color patterns of some reptiles and mammals are found to be consistent with the predictions of the model.

Discrete systems, cell-cell interactions and color pattern of animals. II. Clonal theory and cellular automata.

The morphogenesis of the color pattern of animals is modeled with cellular automata. The cell-cell near neighbor interactions are taken into account and impose restrictions on the model. The allowed patterns are observed in reptiles, felines and fishes.