Abstract P-23: Histone N-terminal Tails Reduce Early Nucleosomal Pausing during Transcription

Background: Nucleosomes are the barriers to transcript elongation by RNA polymerase 2 (Pol 2) in vitro and in vivo. Formation and overcoming the barrier are important for transcription regulation. N-terminal tails of core histones do not affect the inner structure of nucleosomal core. However, strongly positively charged tails can interact with the DNA, thereby impeding polymerase progression through the template. Removal of histone tails was shown to facilitate transcription through a nucleosome by both yeast and human Pol 2, and the effect was most noticeable at lower ionic strength (40 mM KCl). In vivo experiments established a new mechanism of overcoming of +1 nucleosomal barrier by removal of histone tails by specific regulative proteinase. As +1 nucleosomal barrier is formed mostly by the promoter-proximal part of the nucleosomal DNA, here we address the effects of histone tails on elongation through this part of the nucleosome. Methods: We have studied the effect of histone tails on transcription by yeast Pol 2 and model enzyme E. coli RNA polymerase utilizing very similar mechanisms of elongation through chromatin. 603 nucleosomes were transcribed in vitro using purified proteins and components. To focus on the proximal part of the nucleosome, transcript elongation was conducted for a limited time and at low ionic strength. Results: For the phosphorylated form of yeast Pol 2 and E. coli RNAP, histone tail removal significantly reduces the strong nucleosome-specific pausing that the yeast polymerase encounters ∼15 bp within the 603 nucleosome and further downstream, leading to both increased traversal of the pause and the accumulation of complexes paused at more distal locations. However, tail removal did not lead to a significant increase in full traversal of either nucleosomal template. The effect of histone tails removal was cognate for both enzymes but differs in detailed effect on the barrier. Conclusion: Histone tails provide a significant part of the nucleosomal barrier to transcript elongation by Pol 2-type mechanism. The effect is very pronounced in the promoter-proximal part of the nucleosomal DNA, suggesting that histone tails could play a role during the regulation of the +1 nucleosomal barrier. The role of Pol 2 CTD phosphorylation and formation of the intranucleosomal loops in the regulation of +1 nucleosomal barrier will also be addressed

Topological semimetal in a fermionic optical lattice

Optical lattices play a versatile role in advancing our understanding of correlated quantum matter. The recent implementation of orbital degrees of freedom in chequerboard and hexagonal optical lattices opens up a new thrust towards discovering novel quantum states of matter, which have no prior analogs in solid state electronic materials. Here, we demonstrate that an exotic topological semimetal emerges as a parity-protected gapless state in the orbital bands of a two-dimensional fermionic optical lattice. The new quantum state is characterized by a parabolic band-degeneracy point with Berry flux $2\pi$, in sharp contrast to the $\pi$ flux of Dirac points as in graphene. We prove that the appearance of this topological liquid is universal for all lattices with D$_4$ point group symmetry as long as orbitals with opposite parities hybridize strongly with each other and the band degeneracy is protected by odd parity. Turning on inter-particle repulsive interactions, the system undergoes a phase transition to a topological insulator whose experimental signature includes chiral gapless domain-wall modes, reminiscent of quantum Hall edge states.Comment: 6 pages, 3 figures and Supplementary Informatio

Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia—a pilot study

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming.Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65–97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission.Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696).Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems

The N-Terminal Amphipathic Helix of the Topological Specificity Factor MinE Is Associated with Shaping Membrane Curvature

Pole-to-pole oscillations of the Min proteins in Escherichia coli are required for the proper placement of the division septum. Direct interaction of MinE with the cell membrane is critical for the dynamic behavior of the Min system. In vitro, this MinE-membrane interaction led to membrane deformation; however, the underlying mechanism remained unclear. Here we report that MinE-induced membrane deformation involves the formation of an amphipathic helix of MinE2–9, which, together with the adjacent basic residues, function as membrane anchors. Biochemical evidence suggested that the membrane association induces formation of the helix, with the helical face, consisting of A2, L3, and F6, inserted into the membrane. Insertion of this helix into the cell membrane can influence local membrane curvature and lead to drastic changes in membrane topology. Accordingly, MinE showed characteristic features of protein-induced membrane tubulation and lipid clustering in in vitro reconstituted systems. In conclusion, MinE shares common protein signatures with a group of membrane trafficking proteins in eukaryotic cells. These MinE signatures appear to affect membrane curvature

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data