Chromatin Modification by PSC Occurs at One PSC per Nucleosome and Does Not Require the Acidic Patch of Histone H2A

Chromatin architecture is regulated through both enzymatic and non-enzymatic activities. For example, the Polycomb Group (PcG) proteins maintain developmental gene silencing using an array of chromatin-based mechanisms. The essential Drosophila PcG protein, Posterior Sex Combs (PSC), compacts chromatin and inhibits chromatin remodeling and transcription through a non-enzymatic mechanism involving nucleosome bridging. Nucleosome bridging is achieved through a combination of nucleosome binding and self-interaction. Precisely how PSC interacts with chromatin to bridge nucleosomes is not known and is the subject of this work. We determine the stoichiometry of PSC-chromatin interactions in compact chromatin (in which nucleosomes are bridged) using Scanning Transmission Electron Microscopy (STEM). We find that full compaction occurs with one PSC per nucleosome. In addition to compacting chromatin, we show that PSC oligomerizes nucleosome arrays. PSC-mediated oligomerization of chromatin occurs at similar stoichiometry as compaction suggesting it may also involve nucleosome bridging. Interactions between the tail of histone H4 and the acidic patch of histone H2A are important for chromatin folding and oligomerization, and several chromatin proteins bind the histone H2A acidic patch. However, mutation of the acidic patch of histone H2A does not affect PSC’s ability to inhibit chromatin remodeling or bridge nucleosomes. In fact, PSC does not require nucleosomes for bridging activity but can bridge naked DNA segments. PSC clusters nucleosomes on sparsely assembled templates, suggesting it interacts preferentially with nucleosomes over bare DNA. This may be due to the ability of PSC to bind free histones. Our data are consistent with a model in which each PSC binds a nucleosome and at least one other PSC to directly bridge nucleosomes and compact chromatin, but also suggest that naked DNA can be included in compacted structures. We discuss how our data highlight the diversity of mechanisms used to modify chromatin architecture.Molecular and Cellular Biolog

Measurements of quantum yields of bromine atoms in the photolysis of bromoform from 266 to 324 nm

The quantum yield for the formation of bromine atoms in the photolysis of bromoform, CHBr_3, has been measured between 266 and 324 nm. For 303 to 306 nm the quantum yields are unity within the experimental uncertainty of the measurements. At longer wavelengths, where the bromoform cross sections decrease rapidly, an apparent trend to slightly lower quantum yields is probably the result of systematic and random errors or incorrect CHBr_3 absorption cross sections. Support for a unit quantum yield for all wavelengths longer than 300 nm comes from the recent theoretical calculations of Peterson and Francisco. At 266 nm the bromine atom quantum yield is 0.76 (±0.03), indicating that at least one additional dissociation channel becomes important at shorter wavelengths. For modeling of the troposphere, it is recommended that a quantum yield of unity be used for wavelengths of 300 nm and longer

Relationship Between Neck Circumference and Cardiometabolic Parameters in HIV-Infected and non–HIV-Infected Adults

OBJECTIVE: Upper body fat is associated with increased cardiometabolic risk. More recently, neck circumference (NC) and/or neck fat have been associated with hyperlipidemia, impaired glucose homeostasis, and hypertension. The objective of this study was to determine whether this relationship is evident in HIV-infected individuals, who often exhibit changes in relative fat distribution, and to determine whether NC is independently associated with carotid intima-media thickness (cIMT) in HIV and non–HIV-infected patients. RESEARCH DESIGN AND METHODS: Body composition, including anthropometrics, visceral adipose tissue assessment by CT, and metabolic parameters, including lipids, cIMT, and oral glucose tolerance test, were measured in 174 men and women with HIV infection and 154 non–HIV-infected subjects. NC was measured in triplicate inferior to the laryngeal prominence. RESULTS: In univariate analysis, NC was significantly and positively related to blood pressure, hemoglobin A1c, glucose, and insulin and significantly and negatively related to HDL cholesterol in HIV-infected individuals and HIV-negative control subjects. NC was significantly associated with cIMT in univariate regression analysis among HIV-infected (r = 0.21, P = 0.006) and non–HIV-infected (r = 0.31, P = 0.0001) patients. This relationship remained significant among non–HIV-infected patients (R2 = 0.45, P < 0.001) but not HIV-infected patients in multivariate modeling controlling for age, sex, race, smoking hypertension, glucose, and lipids. CONCLUSIONS: Among both HIV and non–HIV-infected patients, increased NC is strongly associated with decreased HDL and impaired glucose homeostasis. Among non–HIV-infected subjects, NC also predicts increased cIMT when controlling for traditional risk factors

New York Economic Handbook, 2006

E.B. 2005-1

Charged hadron multiplicity fluctuations in Au+Au and Cu+Cu collisions from sqrt(s_NN) = 22.5 to 200 GeV

A comprehensive survey of event-by-event fluctuations of charged hadron multiplicity in relativistic heavy ions is presented. The survey covers Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV, and Cu+Cu collisions sqrt(s_NN) = 22.5, 62.4, and 200 GeV. Fluctuations are measured as a function of collision centrality, transverse momentum range, and charge sign. After correcting for non-dynamical fluctuations due to fluctuations in the collision geometry within a centrality bin, the remaining dynamical fluctuations expressed as the variance normalized by the mean tend to decrease with increasing centrality. The dynamical fluctuations are consistent with or below the expectation from a superposition of participant nucleon-nucleon collisions based upon p+p data, indicating that this dataset does not exhibit evidence of critical behavior in terms of the compressibility of the system. An analysis of Negative Binomial Distribution fits to the multiplicity distributions demonstrates that the heavy ion data exhibit weak clustering properties.Comment: 464 authors from 60 institutions, 17 pages, 12 figures, 1 table. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Sphingosine-1-Phosphate: Its Pharmacological Regulation and the Treatment of Multiple Sclerosis: A Review Article.

Sphingosine-1-phosphate (S1P), via its G-protein-coupled receptors, is a signaling molecule with important regulatory properties on numerous, widely varied cell types. Five S1P receptors (S1PR1-5) have been identified, each with effects determined by their unique G-protein-driven downstream pathways. The discovery that lymphocyte egress from peripheral lymphoid organs is promoted by S1P via S1PR-1 stimulation led to the development of pharmacological agents which are S1PR antagonists. These agents promote lymphocyte sequestration and reduce lymphocyte-driven inflammatory damage of the central nervous system (CNS) in animal models, encouraging their examination of efficacy in the treatment of multiple sclerosis (MS). Preclinical research has also demonstrated direct protective effects of S1PR antagonists within the CNS, by modulation of S1PRs, particularly S1PR-1 and S1PR-5, and possibly S1PR-2, independent of effects upon lymphocytes. Three of these agents, fingolimod, siponimod and ozanimod have been approved, and ponesimod has been submitted for regulatory approval. In patients with MS, these agents reduce relapse risk, sustained disability progression, magnetic resonance imaging markers of disease activity, and whole brain and/or cortical and deep gray matter atrophy. Future opportunities in the development of more selective and intracellular S1PR-driven downstream pathway modulators may expand the breadth of agents to treat MS

Consonantal Variation in Utah English What El[t]se is Happening[k]

Most research on Utah English phonology has concentrated on vowels COT-CAUGHT merger, CORD-CARD merger, pre-lateral mergers /aɪ/ monophthongization PIN-PEN merge