Polymer reptation and nucleosome repositioning

We consider how beads can diffuse along a chain that wraps them, without becoming displaced from the chain; our proposed mechanism is analogous to the reptation of "stored length" in more familiar situations of polymer dynamics. The problem arises in the case of globular aggregates of proteins (histones) that are wound by DNA in the chromosomes of plants and animals; these beads (nucleosomes) are multiply wrapped and yet are able to reposition themselves over long distances, while remaining bound by the DNA chain.Comment: 9 pages, including 2 figures, to be published in Phys. Rev. Let

Developments and challenges in dermatology: an update from the Interactive Derma Academy (IDeA) 2019

The 2019 Interactive Derma Academy (IDeA) meeting was held in Lisbon, Portugal, 10–12 May, bringing together leading dermatology experts from across Europe, the Middle East and Asia. Over three days, the latest developments and challenges in relation to the pathophysiology, diagnosis, evaluation and management of dermatological conditions were presented, with a particular focus on acne, atopic dermatitis (AD) and actinic keratosis (AK). Interesting clinical case studies relating to these key topics were discussed with attendees to establish current evidence-based best practices. Presentations reviewed current treatments, potential therapeutic approaches and key considerations in the management of acne, AK and AD, and discussed the importance of the microbiome in these conditions, as well as the provision of patient education/support. It was highlighted that active treatment is not always required for AK, depending on patient preferences and clinical circumstances. In addition to presentations, two interactive workshops on the diagnosis and treatment of sexually transmitted infections/diseases (STIs/STDs) presenting to the dermatology clinic, and current and future dermocosmetics were conducted. The potential for misdiagnosis of STIs/STDs was discussed, with dermoscopy and/or reflectance confocal microscopy suggested as useful diagnostic techniques. In addition, botulinum toxin was introduced as a potential dermocosmetic, and the possibility of microbiome alteration in the treatment of dermatological conditions emphasized. Furthermore, several challenges in dermatology, including the use of lasers, the complexity of atopic dermatitis, wound care, use of biosimilars and application of non-invasive techniques in skin cancer diagnosis were reviewed. In this supplement, we provide an overview of the presentations and discussions from the fourth successful IDeA meeting, summarizing the key insights shared by dermatologists from across the globe

Estimating the economic benefits of regional ocean observing systems

We develop a methodology to estimate the potential economic benefits from new investments in regional coastal ocean observing systems in US waters, and apply this methodology to generate preliminary estimates of such benefits. The approach focuses on potential economic benefits from coastal ocean observing information within ten geographic regions encompassing all coastal waters of the United States, and within a wide range of industrial and recreational activities including recreational fishing and boating, beach recreation, maritime transportation, search and rescue operations, spill response, marine hazards prediction, offshore energy, power generation, and commercial fishing. Our findings suggest that annual benefits to users from the deployment of ocean observing systems are likely to run in the multiple $100s of millions of dollars per year. The project results should be considered first-order estimates that are subject to considerable refinement as the parameters of regional observing systems are better defined, and as our understanding of user sectors improves.Funding was provided by the Office of Naval Research under Grant No. N00014-02-1-1037

The discovery of WASP-151b, WASP-153b, WASP-156b: Insights on giant planet migration and the upper boundary of the Neptunian desert

To investigate the origin of the features discovered in the exoplanet population, the knowledge of exoplanets’ mass and radius with a good precision (≲10%) is essential. To achieve this purpose the discovery of transiting exoplanets around bright stars is of prime interest. In this paper, we report the discovery of three transiting exoplanets by the SuperWASP survey and the SOPHIE spectrograph with mass and radius determined with a precision better than 15%. WASP-151b and WASP-153b are two hot Saturns with masses, radii, densities and equilibrium temperatures of 0.31−0.03+0.04 MJ, 1.13−0.03+0.03 RJ, 0.22−0.02+0.03 ρJ and 1290−10+20 K, and 0.39−0.02+0.02 MJ, 1.55−0.08+0.10 RJ, 0.11−0.02+0.02 ρJ and 1700−40+40 K, respectively. Their host stars are early G type stars (with mag V ~ 13) and their orbital periods are 4.53 and 3.33 days, respectively. WASP-156b is a super-Neptune orbiting a K type star (mag V = 11.6). It has a mass of 0.128−0.009+0.010 MJ, a radius of 0.51−0.02+0.02 RJ, a density of 1.0−0.1+0.1 ρJ, an equilibrium temperature of 970−20+30 K and an orbital period of 3.83 days. The radius of WASP-151b appears to be only slightly inflated, while WASP-153b presents a significant radius anomaly compared to a recently published model. WASP-156b, being one of the few well characterized super-Neptunes, will help to constrain the still debated formation of Neptune size planets and the transition between gas and ice giants. The estimates of the age of these three stars confirms an already observed tendency for some stars to have gyrochronological ages significantly lower than their isochronal ages. We propose that high eccentricity migration could partially explain this behavior for stars hosting a short period planet. Finally, these three planets also lie close to (WASP-151b and WASP-153b) or below (WASP-156b) the upper boundary of the Neptunian desert. Their characteristics support that the ultra-violet irradiation plays an important role in this depletion of planets observed in the exoplanet population

Esperanto for histones : CENP-A, not CenH3, is the centromeric histone H3 variant

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres

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

Crystal structure and mechanism of human lysine-specific demethylase-1

The reversible methylation of specific lysine residues in histone tails is crucial in epigenetic gene regulation. LSD1, the first known lysine-specific demethylase, selectively removes monomethyl and dimethyl, but not trimethyl modifications of Lys4 or Lys9 of histone-3. Here, we present the crystal structure of LSD1 at 2.9-Å resolution. LSD1 forms a highly asymmetric, closely packed domain structure from which a long helical 'tower' domain protrudes. The active site cavity is spacious enough to accommodate several residues of the histone tail substrate, but does not appear capable of recognizing the different methylation states of the substrate lysine. This supports the hypothesis that trimethylated lysine is chemically rather than sterically discriminated. We present a biochemical analysis of LSD1 mutants that identifies crucial residues in the active site cavity and shows the importance of the SWIRM and tower domains for catalysis

An Efficient Rule-Based Distributed Reasoning Framework for Resource-bounded Systems

© 2018, The Author(s). Over the last few years, context-aware computing has received a growing amount of attention among the researchers in the IoT and ubiquitous computing community. In principle, context-aware computing transforms a physical environment into a smart space by sensing the surrounding environment and interpreting the situation of the user. This process involves three major steps: context acquisition, context modelling, and context-aware reasoning. Among other approaches, ontology-based context modelling and rule-based context reasoning are widely used techniques to enable semantic interoperability and interpreting user situations. However, implementing rich context-aware applications that perform reasoning on resource-bounded mobile devices is quite challenging. In this paper, we present a context-aware systems development framework for smart spaces, which includes a lightweight efficient rule engine and a wide range of user preferences to reduce the number of rules while inferring personalized contexts. This shows rules can be reduced in order to optimize the inference engine execution speed, and ultimately to reduce total execution time and execution cost

Contributions of Histone H3 Nucleosome Core Surface Mutations to Chromatin Structures, Silencing and DNA Repair

Histone H3 mutations in residues that cluster in a discrete region on the nucleosome surface around lysine 79 of H3 affect H3-K79 methylation, impair transcriptional silencing in subtelomeric chromatin, and reveal distinct contributions of histone H3 to various DNA-damage response and repair pathways. These residues might act by recruitment of silencing and DNA-damage response factors. Alternatively, their location on the nucleosome surface suggests a possible involvement in nucleosome positioning, stability and nucleosome interactions. Here, we show that the yeast H3 mutants hht2-T80A, hht2-K79E, hht2-L70S, and hht2-E73D show normal nucleosome positioning and stability in minichromosomes. However, loss of silencing in a subtelomeric URA3 gene correlates with a shift of the promoter nucleosome, while nucleosome positions and stability in the coding region are maintained. Moreover, the H3 mutants show normal repair of UV lesions by photolyase and nucleotide excision repair in minichromosomes and slightly enhanced repair in the subtelomeric region. Thus, these results support a role of those residues in the recruitment of silencing proteins and argue against a general role in nucleosome organization