The self-assembly of DNA Holliday junctions studied with a minimal model

In this paper, we explore the feasibility of using coarse-grained models to simulate the self-assembly of DNA nanostructures. We introduce a simple model of DNA where each nucleotide is represented by two interaction sites corresponding to the phosphate-sugar backbone and the base. Using this model, we are able to simulate the self-assembly of both DNA duplexes and Holliday junctions from single-stranded DNA. We find that assembly is most successful in the temperature window below the melting temperatures of the target structure and above the melting temperature of misbonded aggregates. Furthermore, in the case of the Holliday junction, we show how a hierarchical assembly mechanism reduces the possibility of becoming trapped in misbonded configurations. The model is also able to reproduce the relative melting temperatures of different structures accurately, and allows strand displacement to occur.Comment: 13 pages, 14 figure

Chandra X-ray Sources in the Collapsed-Core Globular Cluster M30 (NGC 7099)

We report the detection of six discrete, low-luminosity (Lx < 10^33 erg/s) X-ray sources, located within 12 arcsec of the center of the collapsed-core globular cluster M30 (NGC 7099), and a total of 13 sources within the half-mass radius, from a 50 ksec Chandra ACIS-S exposure. Three sources lie within the very small upper limit of 1.9 arcsec on the core radius. The brightest of the three core sources has a luminosity of Lx (0.5-6 keV) = 6x10^32 erg/s and a blackbody-like soft X-ray spectrum, which are both consistent with it being a quiescent low-mass X-ray binary (qLMXB). We have identified optical counterparts to four of the six central sources and a number of the outlying sources, using deep Hubble Space Telescope and ground-based imaging. While the two proposed counterparts that lie within the core may represent chance superpositions, the two identified central sources that lie outside of the core have X-ray and optical properties consistent with being CVs. Two additional sources outside of the core have possible active binary counterparts. We discuss the X-ray source population of M30 in light of its collapsed-core status.Comment: 18 pages, 13 figures (8 color), resubmitted to ApJ after incorporating referee comment

Circadian Rhythms in Resting Metabolic Rate Account for Apparent Daily Rhythms in the Thermic Effect of Food

Acknowledgments We would like to thank Barbara Fielding, Adam Collins, Hayriye Biyikoglu, Alice Brealy, and Paul Jefcoate as well as all the staff at the Surrey Clinical Research Facility for their assistance in running this study. We would also like to thank Graham Horgan from Biomathematics and Statistics Scotland, for input on the modeling and statistical analysis. Financial Support: This study was funded by the Medical Research Council (grant No. MR/P012205/1, The Big Breakfast Study). A.M.J. and P.J.M. acknowledge funding support from the Scottish Government, Rural and Environment Science and Analytical Services Division.Peer reviewedPublisher PD

Stellar Variability in the Globular Cluster Terzan 5

We present the results of a search for variability in and near the core of the metal-rich, obscured globular cluster Terzan 5, using NICMOS on HST. This extreme cluster has approximately solar metallicity and a central density that places it in the upper few percent of all clusters. It is estimated to have the highest interaction rate of any galactic globular cluster. The large extinction towards Terzan 5 and the severe stellar crowding near the cluster center present a substantial observational challenge. Using time series analysis we discovered two variable stars in this cluster. The first is a RRab Lyrae variable with a period of ~0.61 days, a longer period than that of field stars with similar high metallicities. This period is, however, shorter than the average periods of RR Lyraes found in the metal-rich globular clusters NGC 6441, NGC 6388 and 47 Tuc. The second variable is a blue star with a 7-hour period sinusoidal variation and a likely orbital period of 14 hours. This star is probably an eclipsing blue straggler, or (less likely) the infrared counterpart to the low mass X-ray binary known in Terzan 5. Due to the extreme crowding and overlapping Airy profile of the IR PSF, we fall short of our original goal of detecting CVs via Palpha emission and detecting variable infrared emission from the location of the binary MSP in Terzan 5.Comment: 17 pages including 12 figures. Accepted for publication in Ap

Modelling multiscale aspects of colorectal cancer

Colorectal cancer (CRC) is responsible for nearly half a million deaths annually world-wide [11]. We present a series of mathematical models describing the dynamics of the intestinal epithelium and the kinetics of the molecular pathway most commonly mutated in CRC, the Wnt signalling network. We also discuss how we are coupling such models to build a multiscale model of normal and aberrant guts. This will enable us to combine disparate experimental and clinical data, to investigate interactions between phenomena taking place at different levels of organisation and, eventually, to test the efficacy of new drugs on the system as a whole

HST-NICMOS Observations of Terzan 5: Stellar Content and Structure of the Core

We report results from HST-NICMOS imaging of the extremely dense core of the globular cluster Terzan 5. This highly obscured bulge cluster has been estimated to have one of the highest collision rates of any galactic globular cluster, making its core a particularly conducive environment for the production of interacting binary systems. We have reconstructed high-resolution images of the central 19"x19" region of Terzan 5 by application of the drizzle algorithm to dithered NIC2 images in the F110W, F187W, and F187N near-infrared filters. We have used a DAOPHOT/ALLSTAR analysis of these images to produce the deepest color-magnitude diagram (CMD) yet obtained for the core of Terzan 5. We have also analyzed the parallel 11"X11" NIC1 field, centered 30" from the cluster center and imaged in F110W and F160W, and an additional NIC2 field that is immediately adjacent to the central field. This imaging results in a clean detection of the red-giant branch and horizontal branch in the central NIC2 field, and the detection of these plus the main-sequence turnoff and the upper main sequence in the NIC1 field. We have constructed an H versus J-H CMD for the NIC1 field. We obtain a new distance estimate of 8.7 kpc, which places Terzan 5 within less than 1 kpc of the galactic center. We have also determined a central surface-density profile which results in a maximum likelihood estimate of 7.9" +/- 0.6" for the cluster core radius. We discuss the implications of these results for the dynamical state of Terzan 5.Comment: 17 pages, 9 figures, accepted for publication in ApJ, for May 20, 200

Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Unacylated ghrelin, leptin, and appetite display diurnal rhythmicity in lean adults

Constant routine and forced desynchrony protocols typically remove the effects of behavioral/environmental cues to examine endogenous circadian rhythms, yet this may not reflect rhythms of appetite regulation in the real world. It is therefore important to understand these rhythms within the same subjects under controlled diurnal conditions of light, sleep, and feeding. Ten healthy adults (9 M/1 F, means ±SD: age, 30 ± 10 yr; body mass index, 24.1 ± 2.7 kg·m-2) rested supine in the laboratory for 37 h. All data were collected during the final 24 h of this period (i.e., 0800-0800 h). Participants were fed hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200 to 0700 h. Hourly blood samples were collected throughout the 24-h period. Dim light melatonin onset occurred at 2318 ± 46 min. A diurnal rhythm in mean plasma unacylated ghrelin concentration was identified (P = 0.04), with the acrophase occurring shortly after waking (0819), falling to a nadir in the evening with a relative amplitude of 9%. Plasma leptin concentration also exhibited a diurnal rhythm (P < 0.01), with the acrophase occurring shortly after lights-out (0032 h) and the lowest concentrations at midday. The amplitude for this rhythm was 25%. Diurnal rhythms were established in all dimensions of appetite except for sweet preference (P = 0.29), with both hunger (2103 h) and prospective food consumption (1955 h) reaching their peak in the evening before falling to their nadir shortly after waking. Under controlled diurnal conditions, simultaneous measurement of leptin, unacylated ghrelin, and subjective appetite over a 24-h period revealed rhythmicity in appetite regulation in lean, healthy humans.NEW & NOTEWORTHY Simultaneous assessment of subjective appetite, unacylated ghrelin, and leptin was carried out over a continuous 37-h protocol for the first time under conditions of controlled light, sleep, and feeding in healthy, lean adults. Rhythms were observed in unacylated ghrelin, leptin, and components of subjective appetite, such as hunger, prospective consumption, and fullness. Concurrent measurement of rhythms in these variables is important to fully understand the temporal relationships between components of appetite as well as the influence of diurnal factors such as sleep, light, and feeding

Discovery of Two Gravitationally Lensed Quasars with Image Separations of 3 Arcseconds from the Sloan Digital Sky Survey

We report the discovery of two doubly-imaged quasars, SDSS J100128.61+502756.9 and SDSS J120629.65+433217.6, at redshifts of 1.838 and 1.789 and with image separations of 2.86'' and 2.90'', respectively. The objects were selected as lens candidates from the Sloan Digital Sky Survey (SDSS). Based on the identical nature of the spectra of the two quasars in each pair and the identification of the lens galaxies, we conclude that the objects are gravitational lenses. The lenses are complicated; in both systems there are several galaxies in the fields very close to the quasars, in addition to the lens galaxies themselves. The lens modeling implies that these nearby galaxies contribute significantly to the lens potentials. On larger scales, we have detected an enhancement in the galaxy density near SDSS J100128.61+502756.9. The number of lenses with image separation of ~3'' in the SDSS already exceeds the prediction of simple theoretical models based on the standard Lambda-dominated cosmology and observed velocity function of galaxies.Comment: 24 pages, 9 figures, accepted for publication in Ap

Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131- H 30Rx and ST131- H 30R1 Strains

ABSTRACT Escherichia coli sequence type 131 (ST131) predominates globally among multidrug-resistant (MDR) E. coli strains. We used whole-genome sequencing (WGS) to investigate 63 MDR E. coli isolates from 7 North Carolina community hospitals (2010 to 2015). Of these, 39 (62%) represented ST131, including 37 (95%) from the ST131- H 30R subclone: 10 (27%) from its H 30R1 subset and 27 (69%) from its H 30Rx subset. ST131 core genomes differed by a median of 15 (range, 0 to 490) single-nucleotide variants (SNVs) overall versus only 7 within H 30R1 (range, 3 to 12 SNVs) and 11 within H 30Rx (range, 0 to 21). The four isolates with identical core genomes were all H 30Rx. Epidemiological and clinical characteristics did not vary significantly by strain type, but many patients with MDR E. coli or H 30Rx infection were critically ill and had poor outcomes. H 30Rx isolates characteristically exhibited fluoroquinolone resistance and CTX-M-15 production, had a high prevalence of trimethoprim-sulfamethoxazole resistance (89%), sul1 (89%), and dfrA17 (85%), and were enriched for specific virulence traits, and all qualified as extraintestinal pathogenic E. coli . The high overall prevalence of CTX-M-15 appeared to be possibly attributable to its association with the ST131- H 30Rx subclone and IncF[F2:A1:B−] plasmids. Some phylogenetically clustered non-ST131 MDR E. coli isolates also had distinctive serotypes/ fimH types, fluoroquinolone mutations, CTX-M variants, and IncF types. Thus, WGS analysis of our community hospital source MDR E. coli isolates suggested ongoing circulation and differentiation of E. coli ST131 subclones, with clonal segregation of CTX-M variants, other resistance genes, Inc-type plasmids, and virulence genes