Restraining and unleashing chromatin remodelers - structural information guides chromatin plasticity.

Chromatin remodeling enzymes are large molecular machines that guard the genome by reorganizing chromatin structure. They can reposition, space and evict nucleosomes and thus control gene expression, DNA replication and repair. Recent cryo-electron microscopy (cryo-EM) analyses have captured snapshots of various chromatin remodelers as they interact with nucleosomes. In this review, we summarize and discuss the advances made in our understanding of the regulation of chromatin remodelers, the mode of DNA translocation, as well as the influence of associated protein domains and remodeler subunits on the specific functions of chromatin remodeling complexes. The emerging structural information will help our understanding of disease mechanisms and guide our knowledge toward innovative therapeutic interventions. Copyright © 2020 Elsevier Ltd. All rights reserved

Amplitude equations for a system with thermohaline convection

The multiple scale expansion method is used to derive amplitude equations for a system with thermohaline convection in the neighborhood of Hopf and Taylor bifurcation points and at the double zero point of the dispersion relation. A complex Ginzburg-Landau equation, a Newell-Whitehead-type equation, and an equation of the $\phi^4$ type, respectively, were obtained. Analytic expressions for the coefficients of these equations and their various asymptotic forms are presented. In the case of Hopf bifurcation for low and high frequencies, the amplitude equation reduces to a perturbed nonlinear Schr\"odinger equation. In the high-frequency limit, structures of the type of "dark" solitons are characteristic of the examined physical system.Comment: 21 pages, 8 figure

On the validity of mean-field amplitude equations for counterpropagating wavetrains

We rigorously establish the validity of the equations describing the evolution of one-dimensional long wavelength modulations of counterpropagating wavetrains for a hyperbolic model equation, namely the sine-Gordon equation. We consider both periodic amplitude functions and localized wavepackets. For the localized case, the wavetrains are completely decoupled at leading order, while in the periodic case the amplitude equations take the form of mean-field (nonlocal) Schr\"odinger equations rather than locally coupled partial differential equations. The origin of this weakened coupling is traced to a hidden translation symmetry in the linear problem, which is related to the existence of a characteristic frame traveling at the group velocity of each wavetrain. It is proved that solutions to the amplitude equations dominate the dynamics of the governing equations on asymptotically long time scales. While the details of the discussion are restricted to the class of model equations having a leading cubic nonlinearity, the results strongly indicate that mean-field evolution equations are generic for bimodal disturbances in dispersive systems with \O(1) group velocity.Comment: 16 pages, uuencoded, tar-compressed Postscript fil

A simple mechanism for the reversals of Earth's magnetic field

We show that a model, recently used to describe all the dynamical regimes of the magnetic field generated by the dynamo effect in the VKS experiment [1], also provides a simple explanation of the reversals of Earth's magnetic field, despite strong differences between both systems.Comment: update version, with new figure

ggstThe role of tendon microcirculation in Achilles and patellar tendinopathy

Tendinopathy is of distinct interest as it describes a painful tendon disease with local tenderness, swelling and pain associated with sonographic features such as hypoechogenic texture and diameter enlargement. Recent research elucidated microcirculatory changes in tendinopathy using laser Doppler flowmetry and spectrophotometry such as at the Achilles tendon, the patellar tendon as well as at the elbow and the wrist level. Tendon capillary blood flow is increased at the point of pain. Tendon oxygen saturation as well as tendon postcapillary venous filling pressures, determined non-invasively using combined Laser Doppler flowmetry and spectrophotometry, can quantify, in real-time, how tendon microcirculation changes over with pathology or in response to a given therapy. Tendon oxygen saturation can be increased by repetitive, intermittent short-term ice applications in Achilles tendons; this corresponds to 'ischemic preconditioning', a method used to train tissue to sustain ischemic damage. On the other hand, decreasing tendon oxygenation may reflect local acidosis and deteriorating tendon metabolism. Painful eccentric training, a common therapy for Achilles, patellar, supraspinatus and wrist tendinopathy decreases abnormal capillary tendon flow without compromising local tendon oxygenation. Combining an Achilles pneumatic wrap with eccentric training changes tendon microcirculation in a different way than does eccentric training alone; both approaches reduce pain in Achilles tendinopathy. The microcirculatory effects of measures such as extracorporeal shock wave therapy as well as topical nitroglycerine application are to be studied in tendinopathy as well as the critical question of dosage and maintenance. Interestingly it seems that injection therapy using color Doppler for targeting the area of neovascularisation yields to good clinical results with polidocanol sclerosing therapy, but also with a combination of epinephrine and lidocaine

Mechanisms for High-frequency QPOs in Neutron Star and Black Hole Binaries

We explain the millisecond variability detected by Rossi X-ray Timing Explorer (RXTE) in the X-ray emission from a number of low mass X-ray binary systems (Sco X-1, 4U1728-34, 4U1608-522, 4U1636-536, 4U0614+091, 4U1735-44, 4U1820-30, GX5-1 and etc) in terms of dynamics of the centrifugal barrier, a hot boundary region surrounding a neutron star. We demonstrate that this region may experience the relaxation oscillations, and that the displacements of a gas element both in radial and vertical directions occur at the same main frequency, of order of the local Keplerian frequency. We show the importance of the effect of a splitting of the main frequency produced by the Coriolis force in a rotating disk for the interpretation of a spacing between the QPO peaks. We estimate a magnitude of the splitting effect and present a simple formula for the whole spectrum of the split frequencies. It is interesting that the first three lowest-order overtones fall in the range of 200-1200 Hz and match the kHz-QPO frequencies observed by RXTE. Similar phenomena should also occur in Black Hole (BH) systems, but, since the QPO frequency is inversely proportional to the mass of a compact object, the frequency of the centrifugal-barrier oscillations in the BH systems should be a factor of 5-10 lower than that for the NS systems. The X-ray spectrum formed in this region is a result of upscattering of a soft radiation (from a disk and a NS surface) off relatively hot electrons in the boundary layer. We also briefly discuss some alternative QPO models, including a possibility of acoustic oscillations in the boundary layer, the proper stellar rotation, and g-mode disk oscillations.Comment: The paper is coming out in the Astrophysical Journal in the 1st of May issue of 199

Cellulite and extracorporeal Shockwave therapy (CelluShock-2009) - a Randomized Trial

<p>Abstract</p> <p>Background</p> <p>Cellulite is a widespread problem involving females' buttocks and thighs based on the female specific anatomy. Given the higher number of fat cells stored in female fatty tissue in contrast to males, and the aging process of connective tissue leads to an imbalance between lipogenesis and lipolysis with subsequent large fat cells bulging the skin. In addition, microcirculatory changes have been suggested, however remain largely unknown in a controlled clinical setting. We hypothesize that the combination of extracorporeal shockwave and a daily gluteal muscle strength program is superior to the gluteal muscle strength program alone in cellulite.</p> <p>Methods/Design</p> <p>Study design: Randomized-controlled trial. IRB approval was granted at Hannover Medical School, Germany on May 22, 2009. For allocation of participants, a 1:1 ratio randomization was performed using opaque envelopes for the concealment of allocation. Reporting: according to CONSORT 2010. Eligible patients were females aged 18 or over and 65 or younger with cellulite with documented cellulite 1°-4° according to the Nürnberger score. Exclusion criteria were suspected or evident pregnancy, no cellulite, no informed consent or age under 18 years or above 65 years. Patients were recruited by advertisements in local regional newspapers and via the Internet. Analysis: Intention-to-treat. Outcome parameters: a) Photonumeric severity scale, b) Nürnberger Score, c) circumference measurements, d) capillary blood flow, e) tissue oxygen saturation, f) postcapillary venous blood flow. Intervention group: Six sessions of extracorporeal focused shock wave for six sessions (2000 impulses, 0,25 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Control group: Six sessions of sham extracorporeal focused shock wave for six sessions (2000 impulses, 0,01 mJ/m2 every 1-2 weeks) at both gluteal and thigh regions plus a specific gluteal strength exercise training. Follow-up: 12 weeks. Blinding was achieved for all participants enrolled in the trial, the photograph taking the digital images for the primary outcome measure, the two assessors of the outcome measures, all additional health care providers and for the analyst from the biometrical department. Only one researcher (BJ) was aware of the group assignment performing the randomisation and the extracorporeal shock wave therapy.</p> <p>Discussion</p> <p>This randomised-controlled trial will provide much needed evidence on the clinical effectiveness of focused extracorporal shock wave therapy as an adjunct to gluteal strength training in females suffering cellulite.</p> <p>ClinicalTrials.gov identifier</p> <p>NCT00947414</p

Buoyancy-induced time delays in Babcock-Leighton flux-transport dynamo models

The Sun is a magnetic star whose cyclic activity is thought to be linked to internal dynamo mechanisms. A combination of numerical modelling with various levels of complexity is an efficient and accurate tool to investigate such intricate dynamical processes. We investigate the role of the magnetic buoyancy process in 2D Babcock-Leighton dynamo models, by modelling more accurately the surface source term for poloidal field. Methods. To do so, we reintroduce in mean-field models the results of full 3D MHD calculations of the non-linear evolution of a rising flux tube in a convective shell. More specifically, the Babcock-Leighton source term is modified to take into account the delay introduced by the rise time of the toroidal structures from the base of the convection zone to the solar surface. We find that the time delays introduced in the equations produce large temporal modulation of the cycle amplitude even when strong and thus rapidly rising flux tubes are considered. Aperiodic modulations of the solar cycle appear after a sequence of period doubling bifurcations typical of non-linear systems. The strong effects introduced even by small delays is found to be due to the dependence of the delays on the magnetic field strength at the base of the convection zone, the modulation being much less when time delays remain constant. We do not find any significant influence on the cycle period except when the delays are made artificially strong. A possible new origin of the solar cycle variability is here revealed. This modulated activity and the resulting butterfly diagram are then more compatible with observations than what the standard Babcock-Leighton model produces.Comment: 13 pages, 10 figures, accepted for publication in A&