Inferring the in vivo looping properties of DNA

The free energy of looping DNA by proteins and protein complexes determines to what extent distal DNA sites can affect each other. We inferred its in vivo value through a combined computational-experimental approach for different lengths of the loop and found that, in addition to the intrinsic periodicity of the DNA double helix, the free energy has an oscillatory component with about half the helical period. Moreover, the oscillations have such an amplitude that the effects of regulatory molecules become strongly dependent on their precise DNA positioning and yet easily tunable by their cooperative interactions. These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought.Comment: 20 pages, 4 figure

Lac repressor mediated DNA looping: Monte Carlo simulation of constrained DNA molecules complemented with current experimental results

Tethered particle motion (TPM) experiments can be used to detect time-resolved loop formation in a single DNA molecule by measuring changes in the length of a DNA tether. Interpretation of such experiments is greatly aided by computer simulations of DNA looping which allow one to analyze the structure of the looped DNA and estimate DNA-protein binding constants specific for the loop formation process. We here present a new Monte Carlo scheme for accurate simulation of DNA configurations subject to geometric constraints and apply this method to Lac repressor mediated DNA looping, comparing the simulation results with new experimental data obtained by the TPM technique. Our simulations, taking into account the details of attachment of DNA ends and fluctuations of the looped subsegment of the DNA, reveal the origin of the double-peaked distribution of RMS values observed by TPM experiments by showing that the average RMS value for anti-parallel loop types is smaller than that of parallel loop types. The simulations also reveal that the looping probabilities for the anti-parallel loop types are significantly higher than those of the parallel loop types, even for loops of length 600 and 900 base pairs, and that the correct proportion between the heights of the peaks in the distribution can only be attained when loops with flexible Lac repressor conformation are taken into account. Comparison of the in silico and in vitro results yields estimates for the dissociation constants characterizing the binding affinity between O1 and Oid DNA operators and the dimeric arms of the Lac repressor. © 2014 Biton et al

Social Darwinism in Anglophone Academic Journals: A Contribution to the History of the Term

This essay is a partial history of the term ‘Social Darwinism’. Using large electronic databases, it is shown that the use of the term in leading Anglophone academic journals was rare up to the 1940s. Citations of the term were generally disapproving of the racist or imperialist ideologies with which it was associated. Neither Herbert Spencer nor William Graham Sumner were described as Social Darwinists in this early literature. Talcott Parsons (1932, 1934, 1937) extended the meaning of the term to describe any extensive use of ideas from biology in the social sciences. Subsequently, Richard Hofstadter (1944) gave the use of the term a huge boost, in the context of a global anti-fascist war.Peer reviewe