DNA Conformational Changes and Phase Transitions Induced by Tension and Twist

DNA is a double stranded helical molecule with an intrinsic right handed twist. Its structure can be changed by applying forces and torques in single molecule experiments. In these experiments DNA has been seen to form super-helical structures (supercoils), collapse into tightly condensed states (toroids) and undergo structural changes (phase transitions). Our work focuses on studying all these phenomena by accounting for DNA elasticity, entropic effects due to thermal fluctuations and electrostatics. First, we study the DNA compaction problem in super-helices and toroidal structures. To do so we combine a fluctuating elastic rod model of DNA with electrostatic models for DNA-DNA interactions. Our models are able to predict the onset of the transition to supercoils and toroids under a wide range of experimental conditions. Next, we address DNA phase changes in the presence of mechanical loads.A phenomenon well known from experiments is the overstretching transition associated with the sudden change of DNA extension at high tensions. Depending on the ionic concentration, temperature and pulling rate, DNA can either transform into a melted state (inner strand separation) or S-DNA. Motivated by this, we study the equilibrium and kinetics of the DNA overstretching transitions making use of a quartic potential and non-gaussian integrals to evaluate the free energy of the system. We find that the cooperativity of the transition is a key variable that characterizes the overstretched state. In a separate study we make use of a heterogeneous fluctuating rod model to examine the hypothesis that a newly discovered left-handed form called L-DNA is a mixture of two relatively well-characterized DNA phases - S-DNA and Z-DNA. L-DNA is stable at high tensions and negative twist. We show that if the idea of a mixed state is correct, then the content of S-DNA and Z-DNA varies as a function of the ionic concentration. Finally, we also use our fluctuating rod model to study the mechanical properties of drug-DNA complexes. We show that our methods can predict the results of experiments from various labs if we use only one set of experiments to fit the data to our model

Equilibrium and Kinetics of DNA Overstretching Modeled with a Quartic Energy Landscape

AbstractIt is well known that the dsDNA molecule undergoes a phase transition from B-DNA into an overstretched state at high forces. For some time, the structure of the overstretched state remained unknown and highly debated, but recent advances in experimental techniques have presented evidence of more than one possible phase (or even a mixed phase) depending on ionic conditions, temperature, and basepair sequence. Here, we present a theoretical model to study the overstretching transition with the possibility that the overstretched state is a mixture of two phases: a structure with portions of inner strand separation (melted or M-DNA), and an extended phase that retains the basepair structure (S-DNA). We model the double-stranded DNA as a chain composed of n segments of length l, where the transition is studied by means of a Landau quartic potential with statistical fluctuations. The length l is a measure of cooperativity of the transition and is key to characterizing the overstretched phase. By analyzing the different values of l corresponding to a wide spectrum of experiments, we find that for a range of temperatures and ionic conditions, the overstretched form is likely to be a mix of M-DNA and S-DNA. For a transition close to a pure S-DNA state, where the change in extension is close to 1.7 times the original B-DNA length, we find l ≈ 25 basepairs regardless of temperature and ionic concentration. Our model is fully analytical, yet it accurately reproduces the force-extension curves, as well as the transient kinetic behavior, seen in DNA overstretching experiments

A Computational Model of Protein Induced Membrane Morphology with Geodesic Curvature Driven Protein-Membrane Interface

Continuum or hybrid modeling of bilayer membrane morphological dynamics induced by embedded proteins necessitates the identification of protein-membrane interfaces and coupling of deformations of two surfaces. In this article we developed (i) a minimal total geodesic curvature model to describe these interfaces, and (ii) a numerical one-one mapping between two surface through a conformal mapping of each surface to the common middle annulus. Our work provides the first computational tractable approach for determining the interfaces between bilayer and embedded proteins. The one-one mapping allows a convenient coupling of the morphology of two surfaces. We integrated these two new developments into the energetic model of protein-membrane interactions, and developed the full set of numerical methods for the coupled system. Numerical examples are presented to demonstrate (1) the efficiency and robustness of our methods in locating the curves with minimal total geodesic curvature on highly complicated protein surfaces, (2) the usefulness of these interfaces as interior boundaries for membrane deformation, and (3) the rich morphology of bilayer surfaces for different protein-membrane interfaces

SDSS-IV MaNGA: Evidence for enriched accretion onto satellite galaxies in dense environments

We investigate the environmental dependence of the local gas-phase metallicity in a sample of star-forming galaxies from the MaNGA survey. Satellite galaxies with stellar masses in the range $910^{10.5} \, \mathrm{M_{\odot}}$) centrals are $\sim 0.1 \, \mathrm{dex}$ more metal rich than satellites of low-mass ($M_{*} < 10^{10} \, \mathrm{M_{\odot}}$) centrals, controlling for local stellar mass surface density and gas fraction. Fitting a gas-regulator model to the spaxel data, we are able to account for variations in the local gas fraction, stellar mass surface density and local escape velocity-dependent outflows. We find that the best explanation for the metallicity differences is the variation in the average metallicity of accreted gas between different environments that depends on the stellar mass of the dominant galaxies in each halo. This is interpreted as evidence for the exchange of enriched gas between galaxies in dense environments that is predicted by recent simulations

Unravelling the 2D self-assembly of Fmoc-dipeptides at fluid interfaces

Dipeptides self-assemble into supramolecular structures showing plenty of applications in the nanotechnology and biomedical fields. A set of Fmoc-dipeptides with different aminoacid sequences has been synthesized and their self-assembly at fluid interfaces has been assessed. The relevant molecular parameters for achieving an efficient 2D self-assembly process have been established. The selfassembled nanostructures of Fmoc-dipeptides displayed significant chirality and retained the chemical functionality of the aminoacids. The impact of the sequence on the final supramolecular structure has been evaluated in detail using in situ characterization techniques at air/water interfaces. This study provides a general route for the 2D self-assembly of Fmoc-dipeptides

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

Marvin : a tool kit for streamlined access and visualization of the SDSS-IV MaNGA data set

The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, one of three core programs of the fourth-generation Sloan Digital Sky Survey (SDSS-IV), is producing a massive, high-dimensional integral field spectroscopic data set. However, leveraging the MaNGA data set to address key questions about galaxy formation presents serious data-related challenges due to the combination of its spatially interconnected measurements and sheer volume. For each galaxy, the MaNGA pipelines produce relatively large data files to preserve the spatial correlations of the spectra and measurements, but this comes at the expense of storing the data set in coarse units or "chunks." This coarse chunking and the total volume of the data make it time-consuming to download and curate locally stored data. Thus, accessing, querying, visually exploring, and performing statistical analyses across the whole data set at a fine-grained scale is extremely challenging using just FITS files. To overcome these challenges, we have developed Marvin, a toolkit consisting of a Python package, Application Programming Interface, and web application utilizing a remote database. Marvin allows users to seamlessly work with MaNGA data by abstracting both remote and local (on-disk) interactions to behind-the-scenes data-handling functions. Combining this capability with additional processing and querying tools, users can create powerful Python workflows that are easy to import and share. Marvin's web application uses these tools to enable "point-and-click" examination of data cubes and derived maps, as well as search queries for all publicly released MaNGA galaxies. Marvin's robust and sustainable design minimizes maintenance, while facilitating user-contributed extensions such as high-level analysis code.Publisher PDFPeer reviewe

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar, and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.Fil: Abdurro'Uf, null. Academia Sinica, Institute Of Astronomy And Astrophysics; ChinaFil: Accetta, Katherine. Prynceton University, ; Estados UnidosFil: Aerts, Conny. Katholikie Universiteit Leuven; BélgicaFil: Silva Aguirre, Víctor. Aarhus University. Department of Bioscience; DinamarcaFil: Ahumada, Romina. Universidad Católica del Norte; ChileFil: Ajgaonkar, Nikhil. University of Kentucky; Estados UnidosFil: Filiz Ak, N.. Erciyes University; TurquíaFil: Alam, Shadab. University of Edinburgh; Reino UnidoFil: Allende Prieto, Carlos. Instituto de Astrofísica de Canarias, Tenerife; EspañaFil: Almeida, Andrés. University of Virginia; Estados UnidosFil: Anders, Friedrich. Leibniz-Institut fur Astrophysik Potsdam; AlemaniaFil: Anderson, Scott F.. University of Washington; Estados UnidosFil: Andrews, Brett H.. University of Pittsburgh; Estados UnidosFil: Anguiano, Borja. University of Virginia; Estados UnidosFil: Aquino Ortiz, Erik. Universidad Nacional Autónoma de México; MéxicoFil: Aragón Salamanca, Alfonso. University of Nottingham; Estados UnidosFil: Argudo Fernández, Maria. Pontificia Universidad Católica de Valparaíso; ChileFil: Ata, Metin. University of Tokyo; JapónFil: Aubert, Marie. Aix Marseille Université; FranciaFil: Avila Reese, Vladimir. Universidad Nacional Autónoma de México; MéxicoFil: Badenes, Carles. University of Pittsburgh; Estados UnidosFil: Barbá, Rodolfo. Universidad de La Serena; ChileFil: Barger, Kat. Texas Christian University; Estados UnidosFil: Barrera Ballesteros, Jorge K,. Universidad Nacional Autónoma de México; MéxicoFil: Beaton, Rachael L.. Princeton University; Estados UnidosFil: Beers, Timothy C.. University of Notre Dame; Estados UnidosFil: Belfiore, Francesco. Istituto Nazionale di Astrofisica; ItaliaFil: Bender, Chad F.. University of Arizona; Estados UnidosFil: Bernardi, Mariangela. State University of Pennsylvania; Estados UnidosFil: Bershady, Matthew A.. University of Wisconsin; Estados UnidosFil: Monachesi, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad de La Serena; ChileFil: Padilla, Nelson David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentin

Modified Needle-Tip PcrV Proteins Reveal Distinct Phenotypes Relevant to the Control of Type III Secretion and Intoxication by Pseudomonas aeruginosa

The type III secretion system (T3SS) is employed to deliver effector proteins to the cytosol of eukaryotic hosts by multiple species of Gram-negative bacteria, including Pseudomonas aeruginosa. Translocation of effectors is dependent on the proteins encoded by the pcrGVHpopBD operon. These proteins form a T3S translocator complex, composed of a needle-tip complex (PcrV), translocons (PopB and PopD), and chaperones (PcrG and PcrH). PcrV mediates the folding and insertion of PopB/PopD in host plasmic membranes, where assembled translocons form a translocation channel. Assembly of this complex and delivery of effectors through this machinery is tightly controlled by PcrV, yet the multifunctional aspects of this molecule have not been defined. In addition, PcrV is a protective antigen for P. aeruginosa infection as is the ortholog, LcrV, for Yersinia. We constructed PcrV derivatives containing in-frame linker insertions and site-specific mutations. The expression of these derivatives was regulated by a T3S-specific promoter in a pcrV-null mutant of PA103. Nine derivatives disrupted the regulation of effector secretion and constitutively released an effector protein into growth medium. Three of these regulatory mutants, in which the linker was inserted in the N-terminal globular domain, were competent for the translocation of a cytotoxin, ExoU, into eukaryotic host cells. We also isolated strains expressing a delayed-toxicity phenotype, which secrete translocators slowly despite the normal level of effector secretion. Most of the cytotoxic translocation-competent strains retained the protective epitope of PcrV derivatives, and Mab166 was able to protect erythrocytes during infection with these strains. The use of defined PcrV derivatives possessing distinct phenotypes may lead to a better understanding of the functional aspects of T3 needle-tip proteins and the development of therapeutic agents or vaccines targeting T3SS-mediated intoxication