General guidelines for the molecular basis of functional variation are presented while focused on the rotating circular genetic code and allowable exchanges that make it resistant to genetic diseases under normal conditions. The rules of variation, bioinformatics aids for preventive medicine, are: (1) same position in the four quadrants for hydrophobic codons, (2) same or contiguous position in two quadrants for synonymous or related codons, and (3) same quadrant for equivalent codons. To preserve protein function, amino acid exchange according to the first rule takes into account the positional homology of essential hydrophobic amino acids with every codon with a central uracil in the four quadrants, the second rule includes codons for identical, acidic, or their amidic amino acids present in two quadrants, and the third rule, the smaller, aromatic, stop codons, and basic amino acids, each in proximity within a 90 degree angle. I also define codifying genes and palindromati, CTCGTGCCGAATTCGGCACGAG.

Obesity is a major risk factor for diabetes and heart disease. We previously reported that the inactivation of the gene for perilipin (plin), an adipocyte lipid droplet surface protein, produced lean and obesity-resistant mice. To dissect the underlying mechanisms involved, we used oligonucleotide microarrays to analyze the gene-expression profile of white adipose tissue (WAT), liver, heart, skeletal muscle, and kidney of plin ؊/؊ and plin ϩ/ϩ mice. As compared with wild-type littermates, the WAT of plin ؊/؊ mice had 270 and 543 transcripts that were significantly up-or downregulated. There was a coordinated upregulation of genes involved in ␤-oxidation, the Krebs cycle, and the electron transport chain concomitant with a downregulation of genes involved in lipid biosynthesis. There was also a significant downregulation of the stearoyl CoA desaturase-1 gene, which has been associated with obesity resistance. Thus, in response to the constitutive activation of lipolysis associated with absence of perilipin, WAT activated pathways to rid itself of the products of lipolysis and activated pathways of energy expenditure that contribute to the observed obesity resistance. The biochemical pathways involved in obesity resistance in plin ؊/؊ mice identified in this study may represent potential targets for the treatment of obesity. Diabetes 52:2666 -2674, 2003 P erilipin (plin) is a member of a family of proteins that coat the surfaces of intracellular neutral lipid storage droplets, mainly in adipocytes and in steroidogenic cells (1,2). Perilipin, in the basal state, prevents access of hormone-sensitive lipase to the lipid droplet (3) and is a major substrate of cAMPdependent protein kinase in adipocytes (4). Specific hormonal or cytokine stimuli, such as catecholamines and tumor necrosis factor-␣, activate lipolysis by phosphorylating perilipin, thereby allowing hormone-sensitive lipase to access the lipid droplet and initiate its lipolytic action (5,6).Plin Ϫ/Ϫ mice are characterized by constitutive lipolysis, normal body weight despite an increase in food consumption, a lean body habitus, and smaller fat depots composed of small adipocytes (7,8). These mice display increased oxygen consumption and are resistant to diet-induced and genetic obesity (7).To explain this phenotype, we hypothesized that there had to be significant changes in the expression of genes involved in pathways for substrate and energy metabolism. We further reasoned that although perilipin is expressed in adipocytes, there should be concomitant changes in other tissues that are important in whole-body metabolism, such as the liver, skeletal muscle, heart, and kidney, to explain the profound changes seen in plin Ϫ/Ϫ mice. To test these hypotheses, we performed oligonucleotide microarray analysis of the above tissues of plin Ϫ/Ϫ mice and compared the data with those obtained from their wild-type littermates. We show a concomitant and coordinated upregulation of multiple genes involved in oxidative catabolic pathways along with downregulation of gene...

The main focus of this article is to present the practical aspect of the code rules of variation and the search for a second set of genomic rules, including comparison of sequences to understand how to preserve compatible organisms in danger of extinction and how to generate biodiversity. Three new rules of variation are introduced: 1) homologous recombination, 2) a healthy fertile offspring, and 3) comparison of compatible genomes. The novel search in the natural world for fully compatible genomes capable of homologous recombination is explored by using examples of human polymorphisms in the LDLRAP1 gene, and by the production of fertile offspring by crossbreeding. Examples of dogs, llamas and finches will be presented by a rational control of: natural crossbreeding of organisms with compatible genomes (something already happening in nature), the current work focuses on the generation of new varieties after a careful plan. This study is presented within the context of biosemiotics, which studies the processing of information, signaling and signs by living systems. I define a group of organisms having compatible genomes as a single theme: the genomic species or population, able to speak the same molecular language through different accents, with each variety within a theme being a different version of the same book. These studies have a molecular, compatible genetics context. Population and ecosystem biosemiotics will be exemplified by a possible genetic damage capable of causing mutations by breaking the rules of variation through the coordinated patterns of atoms present in the 9/11 World Trade Center contaminated dust (U, Ba, La, Ce, Sr, Rb, K, Mn, Mg, etc.), combination that may be able to overload the molecular quality control mechanisms of the human body. I introduce here the balance of codons in the circular genetic code: 2[1(1)+1(3)+1(4)+4(2)]=2[2(2)+3(4)]. KeywordsCompatibility; Genetics; Fertility; Genes; Descendants; Mendel; Bateson; WTC; Strontium "…a detailed understanding of the natural order." b Graeser, Lynn, Schoenheit