Use of a distant reporter group as evidence for a conformational change in a sensory receptor

A highly sensitive method for demonstrating ligand-induced conformational changes in protein molecules in solution is described. The method utilizes an environmentally sensitive reporter group that is known to be distant from the active site. In the present application a conformational change is demonstrated in the galactose receptor of Salmonella typhimurium, involved in bacterial sensing and transport, by means of an extrinsic fluorophore, 5-iodoacetamidofluorescein, attached at a single methionine residue, and the intrinsic tryptophan fluorophore. Binding of the ligand galactose perturbs the microenvironment of both the fluorescein and tryptophan, as shown by both spectral and potassium iodide quenching changes. The distance between the two dyes is established by fluorescence energy transfer methods to be 41 ± 10 angstrom. Since only one molecule of galactose binds per molecule of receptor and since the galactose molecule is only about 5 angstrom in length, changes at one of these sites reflect the result of an indirect effect. Hence, there must be a ligand-induced conformational change that is propagated a minimum of 30 angstrom through the receptor molecule

Rocket and FUSE Observations of IC 405: Differential Extinction and Fluorescent Molecular Hydrogen

We present far-ultraviolet spectroscopy of the emission/reflection nebula IC 405 obtained by a rocket-borne long-slit spectrograph and the Far Ultraviolet Spectroscopic Explorer. Both data sets show a rise in the ratio of the nebular surface brightness to stellar flux (S/F_*) of approximately two orders of magnitude towards the blue end of the far-UV bandpass. Scattering models using simple dust geometries fail to reproduce the observed S/F_* for realistic grain properties. The high spectral resolution of the FUSE data reveals a rich fluorescent molecular hydrogen spectrum ~1000" north of the star that is clearly distinguished from the steady blue continuum. The S/F_* remains roughly constant at all nebular pointings, showing that fluorescent molecular hydrogen is not the dominant cause for the blue rise. We discuss three possible mechanisms for the ``Blue Dust'': differential extinction of the dominant star (HD 34078), unusual dust grain properties, and emission from nebular dust. We conclude that uncertainties in the nebular geometry and the degree of dust clumping are most likely responsible for the blue rise. As an interesting consequence of this result, we consider how IC 405 would appear in a spatially unresolved observation. If IC 405 was observed with a spatial resolution of less than 0.4 pc, for example, an observer would infer a far-UV flux that was 2.5 times the true value, giving the appearance of a stellar continuum that was less extinguished than radiation from the surrounding nebula, an effect that is reminiscent of the observed ultraviolet properties of starburst galaxies.Comment: 8 pages, 9 figures, using emulateapj, ApJ - accepte

Targeted colonic release formulations of mesalazine - A clinical pharmaco-scintigraphic proof-of-concept study in healthy subjects and patients with mildly active ulcerative colitis.

Colonic targeting of orally applied therapeutic drugs remains a challenge. Tablet coatings relying on gastrointestinal pH and colonic bacterial enzymes as triggers in association with an inner alkaline layer are expected to improve targeting efficiency. Mesalazine release from three differently coated tablets labelled with 1 MBq 153Sm was characterised in a single centre, open-label, parallel group study in nineteen healthy subjects and seven patients with mildly active ulcerative colitis. Two semi-organic and one aqueous-based outer coating with different ratios of enteric polymer and resistant starch were tested. All coatings showed comparable release lagtimes in biorelevant dissolution media and were not affected by neutron-activation of the samarium tracer. Mesalazine pharmacokinetics and gamma scintigraphy were used to characterise drug release, anatomical site of tablet disintegration and gastrointestinal transit. Initial tablet disintegration occurred at the ileo-caecal junction or beyond in 92% of the subjects Time to initial tablet disintegration was inversely correlated with maximal plasma concentrations and systemic mesalazine exposure. Although high inter-subject variability precluded detection of differences between solvent types and different enteric polymer to polysaccharide ratios, the dual pH and enzymatic triggered release system in combination with an inner alkaline layer promoted mesalazine release at the target site with high accuracy

Advanced Camera for Surveys Observations of Young Star Clusters in the Interacting Galaxy UGC 10214

We present the first Advanced Camera for Surveys (ACS) observations of young star clusters in the colliding/merging galaxy UGC 10214. The observations were made as part of the Early Release Observation (ERO) program for the newly installed ACS during service mission SM3B for the Hubble Space Telescope (HST). Many young star clusters can be identified in the tails of UGC 10214, with ages ranging from ~3 Myr to 10 Myr. The extreme blue V-I (F606W-F814W) colors of the star clusters found in the tail of UGC 10214 can only be explained if strong emission lines are included with a young stellar population. This has been confirmed by our Keck spectroscopy of some of these bright blue stellar knots. The most luminous and largest of these blue knots has an absolute magnitude of M_V = -14.45, with a half-light radius of 161 pc, and if it is a single star cluster, would qualify as a super star cluster (SSC). Alternatively, it could be a superposition of multiple scaled OB associations or clusters. With an estimated age of ~ 4-5 Myr, its derived mass is < 1.3 x 10^6 solar masses. Thus the young stellar knot is unbound and will not evolve into a normal globular cluster. The bright blue clusters and associations are much younger than the dynamical age of the tail, providing strong evidence that star formation occurs in the tail long after it was ejected. UGC 10214 provides a nearby example of processes that contributed to the formation of halos and intra-cluster media in the distant and younger Universe.Comment: 6 pages with embedded figures, ApJ in pres

Discovery of Globular Clusters in the Proto-Spiral NGC2915: Implications for Hierarchical Galaxy Evolution

We have discovered three globular clusters beyond the Holmberg radius in Hubble Space Telescope Advanced Camera for Surveys images of the gas-rich dark matter dominated blue compact dwarf galaxy NGC2915. The clusters, all of which start to resolve into stars, have M_{V606} = -8.9 to -9.8 mag, significantly brighter than the peak of the luminosity function of Milky Way globular clusters. Their colors suggest a metallicity [Fe/H] ~ -1.9 dex, typical of metal-poor Galactic globular clusters. The specific frequency of clusters is at a minimum normal, compared to spiral galaxies. However, since only a small portion of the system has been surveyed it is more likely that the luminosity and mass normalized cluster content is higher, like that seen in elliptical galaxies and galaxy clusters. This suggests that NGC2915 resembles a key phase in the early hierarchical assembly of galaxies - the epoch when much of the old stellar population has formed, but little of the stellar disk. Depending on the subsequent interaction history, such systems could go on to build-up larger elliptical galaxies, evolve into normal spirals, or in rare circumstances remain suspended in their development to become systems like NGC2915.Comment: ApJ Letters accepted; 6 pages, 2 figures, 3 table

HST/ACS weak lensing analysis of the galaxy cluster RDCS 1252.9-2927 at z=1.24

We present a weak lensing analysis of one of the most distant massive galaxy cluster known, RDCS 1252.9-2927 at z=1.24, using deep images from the Advanced Camera for Survey (ACS) on board the Hubble Space Telescope (HST). By taking advantage of the depth and of the angular resolution of the ACS images, we detect for the first time at z>1 a clear weak lensing signal in both the i (F775W) and z (F850LP) filters. We measure a 5-\sigma signal in the i band and a 3-\sigma signal in the shallower z band image. The two radial mass profiles are found to be in very good agreement with each other, and provide a measurement of the total mass of the cluster inside a 1Mpc radius of M(<1Mpc) = (8.0 +/- 1.3) x 10^14 M_\odot in the current cosmological concordance model h =0.70, \Omega_m=0.3, \Omega_\Lambda=0.7, assuming a redshift distribution of background galaxies as inferred from the Hubble Deep Fields surveys. A weak lensing signal is detected out to the boundary of our field (3' radius, corresponding to 1.5Mpc at the cluster redshift). We detect a small offset between the centroid of the weak lensing mass map and the brightest cluster galaxy, and we discuss the possible origin of this discrepancy. The cumulative weak lensing radial mass profile is found to be in good agreement with the X-ray mass estimate based on Chandr and XMM-Newton observations, at least out to R_500=0.5Mpc.Comment: 38 pages, ApJ in press. Full resolution images available at http://www.eso.org/~prosati/RDCS1252/Lombardi_etal_accepted.pd

Internal Color Properties of Resolved Spheroids in the Deep HST/ACS field of UGC 10214

(Abridged) We study the internal color properties of a morphologically selected sample of spheroidal galaxies taken from HST/ACS ERO program of UGC 10214 (``The Tadpole''). By taking advantage of the unprecedented high resolution of the ACS in this very deep dataset we are able to characterize spheroids at sub-arcseconds scales. Using the V_606W and I_814W bands, we construct V-I color maps and extract color gradients for a sample of spheroids at I_814W < 24 mag. We investigate the existence of a population of morphologically classified spheroids which show extreme variation in their internal color properties similar to the ones reported in the HDFs. These are displayed as blue cores and inverse color gradients with respect to those accounted from metallicity variations. Following the same analysis we find a similar fraction of early-type systems (~30%-40%) that show non-homologous internal colors, suggestive of recent star formation activity. We present two statistics to quantify the internal color variation in galaxies and for tracing blue cores, from which we estimate the fraction of non-homogeneous to homogeneous internal colors as a function of redshift up to z<1.2. We find that it can be described as about constant as a function of redshift, with a small increase with redshift for the fraction of spheroids that present strong color dispersions. The implications of a constant fraction at all redshifts suggests the existence of a relatively permanent population of evolving spheroids up to z~1. We discuss the implications of this in the context of spheroidal formation.Comment: Fixed URL for high resolution version. 13 Pages, 10 Figures. Accepted for Publication in ApJ. Sep 1st issue. Higher resolution version and complete table3B at http://acs.pha.jhu.edu/~felipe/e-prints/Tadpol

VLT and ACS observations of RDCS J1252.9-2927: dynamical structure and galaxy populations in a massive cluster at z=1.237

We present results from an extensive spectroscopic survey, carried out with VLT FORS, and from an extensive multiwavelength imaging data set from the HST Advanced Camera for Surveys and ground based facilities, of the cluster of galaxies RDCS J1252.9-2927. We have spectroscopically confirmed 38 cluster members in the redshift range 1.22 < z < 1.25. A cluster median redshift of z=1.237 and a rest-frame velocity dispersion of 747^{+74}_{-84} km/s are obtained. Using the 38 confirmed redshifts, we were able to resolve, for the first time at z > 1, kinematic structure. The velocity distribution, which is not Gaussian at the 95% confidence level, is consistent with two groups that are also responsible for the projected east-west elongation of the cluster. The groups are composed of 26 and 12 galaxies with velocity dispersions of 486^{+47}_{-85} km/s and 426^{+57}_{-105} km/s, respectively. The elongation is also seen in the intracluster gas and the dark matter distribution. This leads us to conclude that RDCS J1252.9-2927 has not yet reached a final virial state. We extend the analysis of the color-magnitude diagram of spectroscopic members to more than 1 Mpc from the cluster center. The scatter and slope of non-[OII]-emitting cluster members in the near-IR red sequence is similar to that seen in clusters at lower redshift. Furthermore, most of the galaxies with luminosities greater than ~ K_s*+1.5 do not show any [OII], indicating that these more luminous, redder galaxies have stopped forming stars earlier than the fainter, bluer galaxies. Our observations provide detailed dynamical and spectrophotometric information on galaxies in this exceptional high-redshift cluster, delivering an in-depth view of structure formation at this epoch only 5 Gyr after the Big Bang.Comment: 29 pages. 16 figures. ApJ accepted. Tables 2,3 and 5, figure 1 and the full figure 5 will be available in the paper and electronic editions from ApJ. v2: minor corrections to the abstract and text to match the Journal's versio

Male Competition Reverses Female Preference For Male Chemical Cues

Females must choose among potential mates with different phenotypes in a variety of social contexts. Many male traits are inherent and unchanging, but others are labile to social context. Competition, for example, can cause physiological changes that reflect recent wins and losses that fluctuate throughout time. We may expect females to respond differently to males depending on the outcome of their most recent fight. In Bolitotherus cornutus (forked fungus beetles), males compete for access to females, but copulation requires female cooperation. In this study, we use behavioral trials to determine whether females use chemical cues to differentiate between males and whether the outcome of recent male competition alters female preference. We measured female association time with chemical cues of two size‐matched males both before and after male–male competition. Females in our study preferred to associate with future losers before males interacted, but changed their preference for realized winners following male competitive interactions. Our study provides the first evidence of change in female preference based solely on the outcome of male–male competition