Cyclin D1 integrates G9a-mediated histone methylation.

Lysine methylation of histones and non-histone substrates by the SET domain containing protein lysine methyltransferase (KMT) G9a/EHMT2 governs transcription contributing to apoptosis, aberrant cell growth, and pluripotency. The positioning of chromosomes within the nuclear three-dimensional space involves interactions between nuclear lamina (NL) and the lamina-associated domains (LAD). Contact of individual LADs with the NL are dependent upon H3K9me2 introduced by G9a. The mechanisms governing the recruitment of G9a to distinct subcellular sites, into chromatin or to LAD, is not known. The cyclin D1 gene product encodes the regulatory subunit of the holoenzyme that phosphorylates pRB and NRF1 thereby governing cell-cycle progression and mitochondrial metabolism. Herein, we show that cyclin D1 enhanced H3K9 dimethylation though direct association with G9a. Endogenous cyclin D1 was required for the recruitment of G9a to target genes in chromatin, for G9a-induced H3K9me2 of histones, and for NL-LAD interaction. The finding that cyclin D1 is required for recruitment of G9a to target genes in chromatin and for H3K9 dimethylation, identifies a novel mechanism coordinating protein methylation

Efficacy of hyaluronate injections in rotator cuff disorders: a level-I meta-analysis

Background: Rotator cuff disease is the most common cause of shoulder pain and weakness. Conservative treatment is the first choice of shoulder pain management. Viscosupplementation of hyaluronic acid (HA) seems to be effective for management of tendon disorders. The objective of this study was to evaluate the scientific evidence reported in literature according to HA shoulder injection in rotator cuff disorders treatment. Methods: An English-language systematic literature search was performed by two independent researchers; data sources included the following databases: MEDLINE, Embase, CINAHL, Google scholar web, Ovid database, Physiotherapy Evidence Database (PEDro), and the Cochrane Library. We performed a broad research for relevant study up to February 2017. Articles were included if they reported data on clinical and functional outcomes in patients who had undergone HA injection for management of rotator cuff pathology compared to placebo, corticosteroid injection and/or physical therapies. Methodological quality was assessed with the PEDro rating scale. The outcomes were improvement of symptoms (assessed by VAS scale) and shoulder function (assessed through DASH and ASES Score). Results: 5 RCTs studies (990 patients) were pooled in the Meta-analysis. The PEDro rating scale ranged from 2 to 8. Two studies compared HA injection with corticosteroid injections, patients were injected once a week for three weeks. Four studies compared HA injection with placebo injection, of which two used 3 weekly injections and two used 5 weekly injections. Significant difference was found in pain reduction between HA and placebo group at 26 weeks follow-up (MD= -0.51, 95% CI -0.96 to -0.07), p=0.02. Conclusion: HA injections might be a valuable safe alternative to other conservative methods for the treatment of rotator cuff disorders. Nowadays, few and low quality randomized controlled trials have been published. Therefore, to reach an overall conclusion about the effect of HA injection in rotator cuff we need more high quality studies. Level of evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Study design: Meta-analys

Three-Dimensional Electronic Structure of type-II Weyl Semimetal WTe2_2

By combining bulk sensitive soft-X-ray angular-resolved photoemission spectroscopy and accurate first-principles calculations we explored the bulk electronic properties of WTe$_2$, a candidate type-II Weyl semimetal featuring a large non-saturating magnetoresistance. Despite the layered geometry suggesting a two-dimensional electronic structure, we find a three-dimensional electronic dispersion. We report an evident band dispersion in the reciprocal direction perpendicular to the layers, implying that electrons can also travel coherently when crossing from one layer to the other. The measured Fermi surface is characterized by two well-separated electron and hole pockets at either side of the $\Gamma$ point, differently from previous more surface sensitive ARPES experiments that additionally found a significant quasiparticle weight at the zone center. Moreover, we observe a significant sensitivity of the bulk electronic structure of WTe$_2$ around the Fermi level to electronic correlations and renormalizations due to self-energy effects, previously neglected in first-principles descriptions

A new doubly discrete analogue of smoke ring flow and the real time simulation of fluid flow

Modelling incompressible ideal fluids as a finite collection of vortex filaments is important in physics (super-fluidity, models for the onset of turbulence) as well as for numerical algorithms used in computer graphics for the real time simulation of smoke. Here we introduce a time-discrete evolution equation for arbitrary closed polygons in 3-space that is a discretisation of the localised induction approximation of filament motion. This discretisation shares with its continuum limit the property that it is a completely integrable system. We apply this polygon evolution to a significant improvement of the numerical algorithms used in Computer Graphics.Comment: 15 pages, 3 figure

Dimensionality-Driven Metal-Insulator Transition in Spin-Orbit-Coupled SrIrO3

Upon reduction of the film thickness we observe a metal-insulator transition in epitaxially stabilized, spin-orbit-coupled SrIrO3 ultrathin films. By comparison of the experimental electronic dispersions with density functional theory at various levels of complexity we identify the leading microscopic mechanisms, i.e., a dimensionality-induced readjustment of octahedral rotations, magnetism, and electronic correlations. The astonishing resemblance of the band structure in the two-dimensional limit to that of bulk Sr2IrO4 opens new avenues to unconventional superconductivity by "clean" electron doping through electric field gating

Conformal Transformations in Cosmology of Modified Gravity: the Covariant Approach Perspective

The 1+3 covariant approach and the covariant gauge-invariant approach to perturbations are used to analyze in depth conformal transformations in cosmology. Such techniques allow us to obtain very interesting insights on the physical content of these transformations, when applied to non-standard gravity. The results obtained lead to a number of general conclusions on the change of some key quantities describing any two conformally related cosmological models. In particular, it is shown that the physics in the Einstein frame has characteristics which are completely different from those in the Jordan frame. Even if some of the geometrical properties of the cosmology are preserved (homogeneous and isotropic Universes are mapped into homogeneous and isotropic universes), it can happen that decelerating cosmologies are mapped into accelerated ones. Differences become even more pronounced when first-order perturbations are considered: from the 1+3 equations it is seen that first-order vector and tensor perturbations are left unchanged in their structure by the conformal transformation, but this cannot be said of the scalar perturbations, which include the matter density fluctuations. Behavior in the two frames of the growth rate, as well as other evolutionary features, like the presence or absence of oscillations, etc., appear to be different too. The results obtained are then explicitly interpreted and verified with the help of some clarifying examples based on $f(R)$-gravity cosmologies.Comment: 26 pages, 8 figure

Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis

Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca2+] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic.The work is supported by an MRC Studentship to JFM and a Wellcome Trust Investigator award to RCH (110158/Z/15/Z), the Leducq Transatlantic Network of Excellence, and the University of Padova Strategico grant (FDL). Part of the study was funded by an MRC Project Grant to TK (MR/P000320/1). Michele Cariello is thanked for help with cyclic voltammetry

CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

Several biomarkers from multiple sclerosis (MS) patients' biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Considering RMS patients with a single demyelinating event, higher concentrations of CHI3L1, CXCL10, CXCL12, and CXCL13 were recorded in patients who converted to clinically defined MS(CDMS). RMS patients in the CXCL13 and CHI3L1 high concentration group had a significantly higher risk of relapse (HR 12.61 and 4.57), MRI activity (HR 7.04 and 2.46), and of any evidence of disease activity (HR 12.13 and 2.90) during follow-up. CSF CXCL13 and CHI3L1 levels represent very good prognostic biomarkers in RMS patients, and therefore can be helpful in the treatment choice. Higher CSF concentrations of neuro-inflammatory biomarkers were associated with a higher risk of conversion to CDMS in patients with a first clinical demyelinating event. Differential CSF BAFF and APRIL levels between RMS and PMS suggest a different modulation of B-cells pathways in the different phases of the disease