How does the chromatin fiber deal with topological constraints?

In the nuclei of eukaryotic cells, DNA is packaged through several levels of compaction in an orderly retrievable way that enables the correct regulation of gene expression. The functional dynamics of this assembly involves the unwinding of the so-called 30 nm chromatin fiber and accordingly imposes strong topological constraints. We present a general method for computing both the twist and the writhe of any winding pattern. An explicit derivation is implemented for the chromatin fiber which provides the linking number of DNA in eukaryotic chromosomes. We show that there exists one and only one unwinding path which satisfies both topological and mechanical constraints that DNA has to deal with during condensation/decondensation processes.Comment: Presented in Nature "News and views in brief" Vol. 429 (13 May 2004). Movies available at http://www.lptl.jussieu.fr/recherche/operationE_fichiers/Page_figurePRL.htm

The Carbon Removal Obligation: Updated analytical model and scenario analysis

The framework for carbon removal obligations (CROs), introduced in ref1, consists of two core mechanisms: (1) the principal CRO mechanism obliges the emitter of a tonne of CO2 to remove a tonne of CO2 from the atmosphere at maturity of the CRO; and (2) the CRO pricing instrument imposes a premium (‘CRO Premium’) on carbon debt, defined as the emissions overshooting the remaining carbon budget. The CRO Premium thus adjusts carbon price levels induced by the principal CRO mechanism to alter the emission profile according to some prespecified preferences. This technical working paper amends and extends the analytical CRO model in two fundamental ways: (1) instead of net emissions we consider gross emissions as basis for carbon debt creation, and gross removals for its compensation. This extends the scope of the principal CRO mechanism and is the basis for disentangling the emission trading system (ETS), that ref1 relies on, from the CDR market; and (2) we introduce the methodology defining the CRO Premium. We deploy the updated analytical framework using a simple numerical model to compute a set of illustrative climate mitigation pathways. Along these scenarios we assess the potential benefits from setting separate targets for emissions reductions and carbon removals – a possibility that results from the disentanglement of the ETS and the CDR market

Constraints, Histones, and the 30 Nanometer Spiral

We investigate the mechanical stability of a segment of DNA wrapped around a histone in the nucleosome configuration. The assumption underlying this investigation is that the proper model for this packaging arrangement is that of an elastic rod that is free to twist and that writhes subject to mechanical constraints. We find that the number of constraints required to stabilize the nuclesome configuration is determined by the length of the segment, the number of times the DNA wraps around the histone spool, and the specific constraints utilized. While it can be shown that four constraints suffice, in principle, to insure stability of the nucleosome, a proper choice must be made to guarantee the effectiveness of this minimal number. The optimal choice of constraints appears to bear a relation to the existence of a spiral ridge on the surface of the histone octamer. The particular configuration that we investigate is related to the 30 nanometer spiral, a higher-order organization of DNA in chromatin.Comment: ReVTeX, 15 pages, 18 figure

Social Cost of Carbon: Systems Analysis Perspective & Relevance to Policy Targets

From the systems analysis perspective, SCC calculation method in DICE is disintegrating the modeled closed system by introducing exogenous emissions. Similar consideration is valid for other SCC calculation methods, where full system linkages cannot be taken into account.Inside DICE, the concept of SCC is implemented by SMAC and there is no practical need to use SCC, which can lead to a policy failure e.g. when used as a tax

Modeling the Emergence of Whisker Direction Maps in Rat Barrel Cortex

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat's face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1

Sequence Effects on DNA Entropic Elasticity

DNA stretching experiments are usually interpreted using the worm-like chain model; the persistence length A appearing in the model is then interpreted as the elastic stiffness of the double helix. In fact the persistence length obtained by this method is a combination of bend stiffness and intrinsic bend effects reflecting sequence information, just as at zero stretching force. This observation resolves the discrepancy between the value of A measured in these experiments and the larger ``dynamic persistence length'' measured by other means. On the other hand, the twist persistence length deduced from torsionally-constrained stretching experiments suffers no such correction. Our calculation is very simple and analytic; it applies to DNA and other polymers with weak intrinsic disorder.Comment: LaTeX; postscript available at http://dept.physics.upenn.edu/~nelson/index.shtm

Mechanical response of plectonemic DNA: an analytical solution

We consider an elastic rod model for twisted DNA in the plectonemic regime. The molecule is treated as an impenetrable tube with an effective, adjustable radius. The model is solved analytically and we derive formulas for the contact pressure, twisting moment and geometrical parameters of the supercoiled region. We apply our model to magnetic tweezer experiments of a DNA molecule subjected to a tensile force and a torque, and extract mechanical and geometrical quantities from the linear part of the experimental response curve. These reconstructed values are derived in a self-contained manner, and are found to be consistent with those available in the literature.Comment: 14 pages, 4 figure