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

Loitering with intent: dealing with human-intensive systems

This paper discusses the professional roles of information systems analysts and users, focusing on a perspective of human intensive, rather than software intensive information systems. The concept of ‘meaningful use’ is discussed in re-lation to measures of success/failure in IS development. The authors consider how a number of different aspects of reductionism may distort analyses, so that processes of inquiry cannot support organizational actors to explore and shape their requirements in relation to meaningful use. Approaches which attempt to simplify complex problem spaces, to render them more susceptible to ‘solution’ are problematized. Alternative perspectives which attempt a systematic, holistic complexification, by supporting contextual dependencies to emerge, are advocated as a way forward

Governments, decentralisation, and the risk of electoral defeat

<p>In the last three decades several countries around the world have transferred authority from their national to their regional governments. However, not all their regions have been empowered to the same degree and important differences can be observed between and within countries. Why do some regions obtain more power than others? Current literature argues that variation in the redistribution of power and resources between regions is introduced by demand. Yet these explanations are conditional on the presence of strong regionalist parties or territorial cleavages. This article proposes instead a theory that links the government’s risk of future electoral defeat with heterogeneous decentralisation, and tests its effects using data from 15 European countries and 141 regions. The results provide evidence that parties in government protect themselves against the risk of electoral defeat by selectively targeting decentralisation towards regions in which they are politically strong. The findings challenge previous research that overestimates the importance of regionalist parties while overlooking differences between regions.</p

Enhancement of Magneto-Optic Effects via Large Atomic Coherence

We utilize the generation of large atomic coherence to enhance the resonant nonlinear magneto-optic effect by several orders of magnitude, thereby eliminating power broadening and improving the fundamental signal-to-noise ratio. A proof-of-principle experiment is carried out in a dense vapor of Rb atoms. Detailed numerical calculations are in good agreement with the experimental results. Applications such as optical magnetometry or the search for violations of parity and time reversal symmetry are feasible

Mechanism Based Design of Efficient PET Hydrolases

Polyethylene terephthalate PET is the most widespread synthetic polyester, having been utilized in textile fibers and packaging materials for beverages and food, contributing considerably to the global solid waste stream and environmental plastic pollution. While enzymatic PET recycling and upcycling have recently emerged as viable disposal methods for a circular plastic economy, only a handful of benchmark enzymes have been thoroughly described and subjected to protein engineering for improved properties over the last 16 years. By analyzing the specific material properties of PET and the reaction mechanisms in the context of interfacial biocatalysis, this Perspective identifies several limitations in current enzymatic PET degradation approaches. Unbalanced enzyme substrate interactions, limited thermostability, and low catalytic efficiency at elevated reaction temperatures, and inhibition caused by oligomeric degradation intermediates still hamper industrial applications that require high catalytic efficiency. To overcome these limitations, successful protein engineering studies using innovative experimental and computational approaches have been published extensively in recent years in this thriving research field and are summarized and discussed in detail here. The acquired knowledge and experience will be applied in the near future to address plastic waste contributed by other mass produced polymer types e.g., polyamides and polyurethanes that should also be properly disposed by biotechnological approache

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length

In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties

Search for the Higgs boson in events with missing transverse energy and b quark jets produced in proton-antiproton collisions at s**(1/2)=1.96 TeV

We search for the standard model Higgs boson produced in association with an electroweak vector boson in events with no identified charged leptons, large imbalance in transverse momentum, and two jets where at least one contains a secondary vertex consistent with the decay of b hadrons. We use ~1 fb-1 integrated luminosity of proton-antiproton collisions at s**(1/2)=1.96 TeV recorded by the CDF II experiment at the Tevatron. We find 268 (16) single (double) b-tagged candidate events, where 248 +/- 43 (14.4 +/- 2.7) are expected from standard model background processes. We place 95% confidence level upper limits on the Higgs boson production cross section for several Higgs boson masses ranging from 110 GeV/c2 to 140 GeV/c2. For a mass of 115 GeV/c2 the observed (expected) limit is 20.4 (14.2) times the standard model prediction.Comment: 8 pages, 2 figures, submitted to Phys. Rev. Let

Colonial Heritage and Economic Development

While the importance of institutions for explaining cross-country income differences is widely recognized, comparatively little is known about the origins of economic institutions. One strand of the literature emphasizes cultural differences while another points at exogenous environmental factors such as mortality and climate. Both are supported by some empirical evidence. I reconcile the two schools of institutional origins by proposing a theory of self-selection of colonists to different geographic destinations. Exogenous characteristics such as climate, mortality and factor differences determine which type of settler decides to move to a particular colony. Settler type, in turn, shapes the institutional quality of the new country. The model is used to confirm observed regularities reported by previous researchers. Furthermore, robust new evidence is presented in support of this selection process. The results suggest that any theory of colonial development that does not take selection into account will be incomplete