Photochemically re-bridging disulfide bonds and the discovery of a thiomaleimide mediated photodecarboxylation of C-terminal cysteines

Described in this work is a novel method for photochemically manipulating peptides and proteins via the installation of cysteine-selective photoactive tags. Thiomaleimides, generated simply by the addition of bromomaleimides to reduced disulfide bonds, undergo [2 + 2] photocycloadditions to reconnect the crosslink between the two cysteine residues. This methodology is demonstrated to enable photoactivation of a peptide by macrocyclisation, and reconnection of the heavy and light chains in an antibody fragment to form thiol stable conjugates. Finally we report on an intriguing thiomaleimide mediated photochemical decarboxylation of C-terminal cysteines, discovered during this study

Towards an accurate model of the redshift space clustering of halos in the quasilinear regime

Observations of redshift-space distortions in spectroscopic galaxy surveys offer an attractive method for measuring the build-up of cosmological structure, which depends both on the expansion rate of the Universe and our theory of gravity. Galaxies occupy dark matter halos, whose redshift space clustering has a complex dependence on bias that cannot be inferred from the behavior of matter. We identify two distinct corrections on quasilinear scales (~ 30-80 Mpc/h): the non-linear mapping between real and redshift space positions, and the non-linear suppression of power in the velocity divergence field. We model the first non-perturbatively using the scale-dependent Gaussian streaming model, which we show is accurate at the <0.5 (2) per cent level in transforming real space clustering and velocity statistics into redshift space on scales s>10 (s>25) Mpc/h for the monopole (quadrupole) halo correlation functions. We use perturbation theory to predict the real space pairwise halo velocity statistics. Our fully analytic model is accurate at the 2 per cent level only on scales s > 40 Mpc/h. Recent models that neglect the corrections from the bispectrum and higher order terms from the non-linear real-to-redshift space mapping will not have the accuracy required for current and future observational analyses. Finally, we note that our simulation results confirm the essential but non-trivial assumption that on large scales, the bias inferred from real space clustering of halos is the same one that determines their pairwise infall velocity amplitude at the per cent level.Comment: 15 pages, 12 figures, submitted to MNRA

Structural requirements of membrane phospholipids for M-type potassium channel activation and binding.

M-channels are voltage-gated potassium channels that regulate cell excitability. They are heterotetrameric assemblies of Kv7.2 and Kv7.3 subunits. Their opening requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)). However, the specificity of PI(4,5)P(2) as a binding and activating ligand is unknown. Here, we tested the ability of different phosphoinositides and lipid phosphates to activate or bind to M-channel proteins. Activation of functional channels was measured in membrane patches isolated from cells coexpressing Kv7.2 and Kv7.3 subunits. Channels were activated to similar extents (maximum open probability of ∼0.8 at 0 mV) by 0.1-300 μM dioctanoyl homologs of the three endogenous phosphoinositides, PI(4)P, PI(4,5)P(2), and PI(3,4,5)P(3), with sensitivity increasing with increasing numbers of phosphates. Non-acylated inositol phosphates had no effect up to 100 μM. Channels were also activated with increasing efficacy by 1-300 μM concentrations of the monoacyl monophosphates fingolimod phosphate, sphingosine 1-phosphate, and lysophosphatidic acid but not by phosphate-free fingolimod or sphingosine or by phosphate-masked phosphatidylcholine or phosphatidylglycerol. An overlay assay confirmed that a fusion protein containing the full-length C terminus of Kv7.2 could bind to a broad range of phosphoinositides and phospholipids. A mutated Kv7.2 C-terminal construct with reduced sensitivity to PI(4,5)P showed significantly less binding to most polyphosphoinositides. We concluded that M-channels bind to, and are activated by, a wide range of lipid phosphates, with a minimum requirement for an acyl chain and a phosphate headgroup. In this, they more closely resemble inwardly rectifying Kir6.2 potassium channels than the more PI(4,5)P(2)-specific Kir2 channels. Notwithstanding, the data also support the view that the main endogenous activator of M-channels is PI(4,5)P(2)

Evolved stars hint to an external origin of enhanced metallicity in planet-hosting stars

Exo-planets are preferentially found around high metallicity main sequence stars. We aim at investigating whether evolved stars share this property, and what this tells about planet formation. Statistical tools and the basic concepts of stellar evolution theory are applied to published results as well as our own radial velocity and chemical analyses of evolved stars. We show that the metal distributions of planet-hosting (P-H) dwarfs and giants are different, and that the latter do not favor metal-rich systems. Rather, these stars follow the same age-metallicity relation as the giants without planets in our sample. The straightforward explanation is to attribute the difference between dwarfs and giants to the much larger masses of giants' convective envelopes. If the metal excess on the main sequence is due to pollution, the effects of dilution naturally explains why it is not observed among evolved stars. Although we cannot exclude other explanations, the lack of any preference for metal-rich systems among P-H giants could be a strong indication of the accretion of metal-rich material. We discuss further tests, as well as some predictions and consequences of this hypothesis.Comment: A&A, in pres

Photometric Properties of Void Galaxies in the Sloan Digital Sky Survey DR7 Data Release

Using the sample presented in Pan:2011, we analyse the photometric properties of 88,794 void galaxies and compare them to galaxies in higher density environments with the same absolute magnitude distribution. In Pan et al. (2011), we found a total of 1054 dynamically distinct voids in the SDSS with radius larger than 10h^-1 Mpc. The voids are underdense, with delta rho/rho < -0.9 in their centers. Here we study the photometric properties of these void galaxies. We look at the u - r colours as an indication of star formation activity and the inverse concentration index as an indication of galaxy type. We find that void galaxies are statistically bluer than galaxies found in higher density environments with the same magnitude distribution. We examine the colours of the galaxies as a function of magnitude, and we fit each colour distribution with a double-Gaussian model for the red and blue subpopulations. As we move from bright to dwarf galaxies, the population of red galaxies steadily decreases and the fraction of blue galaxies increases in both voids and walls, however the fraction of blue galaxies in the voids is always higher and bluer than in the walls. We also split the void and wall galaxies into samples depending on galaxy type. We find that late type void galaxies are bluer than late type wall galaxies and the same holds for early galaxies. We also find that early type, dwarf void galaxies are blue in colour. We also study the properties of void galaxies as a function of their distance from the center of the void. We find very little variation in the properties, such as magnitude, colour and type, of void galaxies as a function of their location in the void. The only exception is that the dwarf void galaxies may live closer to the center. The centers of voids have very similar density contrast and hence all void galaxies live in very similar density environments (ABRIDGED)Comment: 10 pages, 25 figure

Basic physical parameters of a selected sample of evolved stars

We present the detailed spectroscopic analysis of 72 evolved stars, including the [Fe/H] determination for the whole sample. These metallicities, together with the Teff values and the absolute V magnitude derived from Hipparcos parallaxes, are used to estimate basic stellar parameters (ages, masses, radii, (B-V)o and log g using theoretical isochrones and a Bayesian estimation method. The (B-V)o values so estimated turn out to be in excellent agreement with the observed (B-V), confirming the reliability of the (Teff,(B-V)o) relation used in the isochrones. The estimated diameters have been compared with limb darkening-corrected ones measured with independent methods, finding an agreement better than 0.3 mas within the 1-10 mas interval. We derive the age-metallicity relation for the solar neighborhood; for the first time such a relation has been derived from observations of field giants rather than from open clusters and field dwarfs and subdwarfs. The age-metallicity relation is characterized by close-to-solar metallicities for stars younger than ~4 Gyr, and by a large [Fe/H] spread with a trend towards lower metallicities for higher ages. We find that the [Fe/H] dispersion of young stars (less than 1 Gyr) is comparable to the observational errors, indicating that stars in the solar neighbourhood are formed from interstellar matter of quite homogeneous chemical composition. The three giants of our sample which have been proposed to host planets are not metal rich, what is at odds with those for main sequence stars. However, two of these stars have masses much larger than a solar mass so we may be sampling a different stellar population from most radial velocity searches for extrasolar planets. We also confirm that the radial velocity variability tends to increase along the RGB.Comment: 17 pgs, 19 fig

Planetary companions around the K giant stars 11 UMi and HD 32518

11 UMi and HD 32518 belong to a sample of 62 K giant stars that has been observed since February 2004 using the 2m Alfred Jensch telescope of the Th\"uringer Landessternwarte (TLS) to measure precise radial velocities (RVs). The aim of this survey is to investigate the dependence of planet formation on the mass of the host star by searching for planetary companions around intermediate-mass giants. An iodine absorption cell was used to obtain accurate RVs for this study. Our measurements reveal that the RVs of 11 UMi show a periodic variation of 516.22 days. The RV curve of HD 32518 shows sinusoidal variations with a period of 157.54 days. The HIPPARCOS photometry as well as our H\alpha core flux measurements reveal no variability with the RV period. Thus, Keplerian motion is the most likely explanation for the observed RV variations for both giant stars. An exoplanet with a minimum mass of 10.5 Jupiter masses orbits the K giant 11 UMi. The K1 III giant HD 32518 hosts a planetary companion with a minimum mass of 3.0 Jupiter masses in a nearly circular orbit. These are the 4th and 5th planets published from this TLS survey.Comment: 11 pages, 16 figure

Precise radial velocities of giant stars. III. Spectroscopic stellar parameters

Context: A radial velocity survey of about 380 G and K giant stars is ongoing at Lick observatory. For each star we have a high signal to noise ratio template spectrum, which we use to determine spectroscopic stellar parameters. Aim: The aim of this paper is to present spectroscopic stellar parameters, i.e. effective temperature, surface gravity, metallicity and rotational velocity for our sample of G and K giant stars. Methods: Effective temperatures, surface gravities and metallicities are determined from the equivalent width of iron lines. Rotational velocities are determined from the full width at half maximum (FWHM) of moderate spectral lines. A calibration between the FWHM and total broadening (rotational velocity and macro turbulence) is obtained from stars in common between our sample and the sample from Gray (1989). Results: The metallicity we derive is essentially equal to the literature values, while the effective temperature and surface gravity are slightly higher by 56 K and 0.15 dex, respectively. Our rotational velocities are comparable with the ones obtained by Gray (1989), but somewhat higher than the ones obtained by de Medeiros & Mayor (1999), consistent with the different diagnostics used. Conclusions: We are able to determine spectroscopic stellar parameters for about 380 G and K giant stars in a uniform way (112 stars are being analysed spectroscopically for the first time). For stars available in the literature, we find reasonable agreement between literature values and values determined in the present work. In addition, we show that the metallicity enhancement of companion hosting stars might also be valid for giant stars, with the planet-hosting giants being 0.13 +/- 0.03 dex (i.e. 35 +/- 10%) more metal-rich than our total sample of stars.Comment: 16 pages, 8 figures, 4 tables, accepted for publication by Astronomy and Astrophysic

"Freshwater killer whales": beaching behavior of an alien fish to hunt land birds

The behavioral strategies developed by predators to capture and kill their prey are fascinating, notably for predators that forage for prey at, or beyond, the boundaries of their ecosystem. We report here the occurrence of a beaching behavior used by an alien and large-bodied freshwater predatory fish (Silurus glanis) to capture birds on land (i.e. pigeons, Columbia livia). Among a total of 45 beaching behaviors observed and filmed, 28% were successful in bird capture. Stable isotope analyses (δ¹³C and δ¹⁵N) of predators and their putative prey revealed a highly variable dietary contribution of land birds among individuals. Since this extreme behavior has not been reported in the native range of the species, our results suggest that some individuals in introduced predator populations may adapt their behavior to forage on novel prey in new environments, leading to behavioral and trophic specialization to actively cross the water-land interface

Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating

The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel’s selectivity filter and its ability to alter gating, with most studies involving prokaryotic K+ channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K+ channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K+ conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating