Phonon theory of DNA processes--a study of excitations and melting

The DNA molecule is considered as an infinite one dimensional lattice. Its processes are comprehended in terms of phonons traversing the polymer. We commence our understanding of the essential dynamics of the molecule by deriving dispersion relations, i.e. relations between wavelength and frequency of waves in the lattice. The DNA molecule contains information essential for life processes in the sequence of bases in its strands. When this information is sought to be communicated to the cell a partial strand separation is a prerequisite to revealing the code in the base sequence. Replication of DNA requires total strand separation. We have conceived of such strand separation as a melting of hydrogen bonds connecting the two strands. We model the lattice in terms of harmonic force constants and examine the stretching of the hydrogen bonds. Then, we selectively introduce anharmonicity in the hydrogen bond force constants as the temperature increases. This is done through a mean field self consistent phonon approach. The breakdown of self consistency is interpreted as a breakdown of the effective hydrogen bond force constants and hence as melting. To study the relative influences of the A-T and G-C base pairs, we have examined 5 copolymers whose unit cells are GCCG, ACGT, AGCT, ATAT in the B conformation and GCGC in the Z conformation. (Here GCGC implies that the unit cell is composed of two base pairs with a C-G pair following a G-C pair). We find good correlation with experimental results on DNA excitations. By our calculations the mean field melting temperatures in K are 385, 366, 357, 325 for the B-DNA copolymers. Our calculations reveal specific bonds in the unit cell that initiate the melting. This is one step in understanding the significant mechanisms of transcription and replication in the DNA molecule

Resveratrol improves health and survival of mice on a high-calorie diet

Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing

Growth Factor Signals in Neural Cells: COHERENT PATTERNS OF INTERACTION CONTROL MULTIPLE LEVELS OF MOLECULAR AND PHENOTYPIC RESPONSES*S⃞

Individual neurons express receptors for several different growth factors that influence the survival, growth, neurotransmitter phenotype, and other properties of the cell. Although there has been considerable progress in elucidating the molecular signal transduction pathways and physiological responses of neurons and other cells to individual growth factors, little is known about if and how signals from different growth factors are integrated within a neuron. In this study, we determined the interactive effects of nerve growth factor, insulin-like growth factor 1, and epidermal growth factor on the activation status of downstream kinase cascades and transcription factors, cell survival, and neurotransmitter production in neural cells that express receptors for all three growth factors. We document considerable differences in the quality and quantity of intracellular signaling and eventual phenotypic responses that are dependent on whether cells are exposed to a single or multiple growth factors. Dual stimulations that generated the greatest antagonistic or synergistic actions, compared with a theoretically neutral summation of their two activities, yielded the largest eventual change of neuronal phenotype indicated by the ability of the cell to produce norepinephrine or resist oxidative stress. Combined activation of insulin-like growth factor 1 and epidermal growth factor receptors was particularly notable for antagonistic interactions at some levels of signal transduction and norepinephrine production, but potentiation at other levels of signaling and cytoprotection. Our findings suggest that in true physiological settings where multiple growth factors are present, activation of one receptor type may result in molecular and phenotypic responses that are different from that observed in typical experimental paradigms in which cells are exposed to only a single growth factor at a time