A rate distortion approach to protein symmetry

A spontaneous symmetry breaking argument is applied to the problem of protein folding, via a rate distortion analysis of the relation between genome coding and the final condensation of the protein molten globule that is, in spirit, analogous to Tlusty’s (2007) exploration of the evolution of the genetic code. In the ‘energy’ picture, the average distortion between codon message and final protein structure, under constraints driven by evolutionary selection, serves as a temperature analog, so that low values limit the possible distribution of protein forms, producing the canonical folding funnel. A dual ‘developmental’ perspective sees the rate distortion function itself as the temperature analog, and permits incorporation of chaperons or toxic exposures as catalysts, driving the system to different possible outcomes or affecting the rate of convergence. The rate distortion function appears constrained by the availability of metabolic free energy, with implications for prebiotic evolution, and a nonequilibrium empirical Onsager treatment provides an adaptable statistical model that can be fitted to data, in the same manner as a regression equation. In sum, mechanistic models of protein folding fail to account for the observed spectrum of protein folding and aggregation disorders, suggesting that a biologically based cognitive paradigm describing folding will be needed for understanding the etiology, prevention, and treatment of these diseases. The developmental formalism introduced here may contribute substantially to such a paradigm.     

Intrinsic protein fluorescence assays for GEF,GAP and post-translational modifications of small GTPases

Evidence and arguments are summarized that suggest that intrinsic (tryptophan) protein fluorescence provides an excellent and convenient signal for monitoring both GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) activity of a large number of small GTPases. In addition, post-translational modifications of Rab proteins occurring in a region known to be a hot spot for such modifications also lead to fluorescence changes that can be accurately monitored in a time-dependent manner. It is suggested that intrinsic fluorescence should be the first method chosen for monitoring such reactions of tryptophan-containing small GTPases.     

Solitary hypothalamic neurons inherently express vasopressin and tyrosine hydroxylase

Hypothalamic neurons were grown as single cells in three-dimensional culture. Solitary neurons lacking cell contacts were immunocytochemically examined for inherent expression of vasopressin (VP), tyrosine hydroxylase (TH), and luteinizing hormone releasing hormone (LHRH). Immunoreactive VP and TH were detected within a day. Sixty to eighty-five percent of neurons displayed homogeneously distributed reaction product for VP or TH. One percent exhibited intense punctate staining of somas and varicosities. Few neurons stained for LHRH. Results indicate that hypothalamic neurons can express appropriate neuropeptides and transmitter-specific products without contacting other neurons or nonneuronal cells. Thus, this culture system may provide a useful model to study intrinsic neuronal processes.     

Variation due to maternal age in the onion root maggot,Hylemya antiqua (Meigen)

A variety of characteristics were studied in populations of the onion root maggot, Hylemya antiqua, to determine the extent to which the age of the female producing a batch of eggs might affect heterogeneity in her offspring. Early-born offspring were found to be reproductively most successful. They had the longest mean expectation of life, a relatively low mortality rate into mid-life, the highest average fecundity, the highest mean rate of egg production, and they produced the highest percentage of female offspring. On the other hand, mid-born offspring were hardiest. They also had a long mean expectation of life, comparable to that for early-born offspring but, in addition, they had the lowest sustained mortality rate and the greatest ability to survive food stress. Their robustness may have been acquired at the expense of certain reproductive capabilities however, in that their average fecundity was lower than their early-born siblings', and their rate of egg production was more variable. Late-born offspring were the most mortality-prone and the least fecund, but they had the shortest mean generation time. These differences must be evaluated in terms of their effects on the rate of natural increase and on population growth. Maternal age was found to influence pupal size, although the provenance groups differed significantly from each other and, in fact, showed opposite trends within their respective cohort groups. Size itself, and the ability of a species to alter the size at which it pupates, may be characteristics which have evolved to fit a specific set of environmental conditions.     

Estimation of contemporaneous mortality factors

We present methods for solving and making statistical inferences about marginal attack rates based on observed death rates for contemporaneous mortality factors. The general method of solution involves solving a system of nonlinear equations which depend in part on competition coefficients that express the outcome when more than one agent attacks the same host individual. For two factors, we present a detailed analysis of the effect of varying this competition coefficient. Statistical inferences are illustrated using standard large sample approximations (the delta method) and the bootstrap, which is a resampling technique. We also extend the results to allow inferences for k-values.