Structural Coupling Between FKBP12 and Buried Water

Globular proteins often contain structurally well-resolved internal water molecules. Previously, we reported results from a molecular dynamics study that suggested that buried water (Wat3) may play a role in modulating the structure of the FK506 binding protein-12 (FKBP12) (Park and Saven, Proteins 2005; 60:450-463). In particular, simulations suggested that disrupting a hydrogen bond to Wat3 by mutating E60 to either A or Q would cause a structural perturbation involving the distant W59 side chain, which rotates to a new conformation in response to the mutation. This effectively remodels the ligand-binding pocket, as the side chain in the new conformation is likely to clash with bound FK506. To test whether the protein structure is in effect modulated by the binding of a buried water in the distance, we determined high-resolution (0.92-1.29 A) structures of wild-type FKBP12 and its two mutants (E60A, E60Q) by X-ray crystallography. The structures of mutant FKBP12 show that the ligand-binding pocket is indeed remodeled as predicted by the substitution at position 60, even though the water molecule does not directly interact with any of the amino acids of the binding pocket. Thus, these structures support the view that buried water molecules constitute an integral, noncovalent component of the protein structure. Additionally, this study provides an example in which predictions from molecular dynamics simulations are experimentally validated with atomic precision, thus showing that the structural features of protein-water interactions can be reliably modeled at a molecular level

Radio Continuum Emission at 1.4 GHz from KISS Emission-Line Galaxies

We have searched the Faint Images of the Radio Sky at Twenty centimeters (FIRST) and the NRAO VLA Sky Survey (NVSS) 1.4 GHz radio surveys for sources that are coincident with emission-line galaxy (ELG) candidates from the KPNO International Spectroscopic Survey (KISS). A total of 207 of the 2157 KISS ELGs (~10%) in the first two H-alpha-selected survey lists were found to possess radio detections in FIRST and/or NVSS. Follow-up spectra exist for all of the radio detections, allowing us to determine the activity type (star-forming vs. AGN) for the entire sample. We explore the properties of the radio-detected KISS galaxies in order to gain a better insight into the nature of radio-emitting galaxies in the local universe (z < 0.1). No dwarf galaxies were detected, despite the large numbers of low-luminosity galaxies present in KISS, suggesting that lower mass, lower luminosity objects do not possess strong galaxian-scale magnetic fields. Due to the selection technique used for KISS, our radio ELGs represent a quasi-volume-limited sample, which allows us to develop a clearer picture of the radio galaxy population at low redshift. Nearly 2/3rds of the KISS radio galaxies are starburst/star-forming galaxies, which is in stark contrast to the results of flux-limited radio surveys that are dominated by AGNs and elliptical galaxies (i.e., classic radio galaxies). While there are many AGNs among the KISS radio galaxies, there are no objects with large radio powers in our local volume. We derive a radio luminosity function (RLF) for the KISS ELGs that agrees very well with previous RLFs that adequately sample the lower-luminosity radio population.Comment: Accepted for publication in the Astronomical Journal (April 2004); 23 pages, 16 figure

Halo Star Streams in the Solar Neighborhood

We have assembled a sample of halo stars in the solar neighborhood to look for halo substructure in velocity and angular momentum space. Our sample includes red giants, RR Lyrae, and red horizontal branch stars within 2.5 kpc of the Sun with [Fe/H] less than -1.0. It was chosen to include stars with accurate distances, space velocities, and metallicities as well as well-quantified errors. We confirm the existence of the streams found by Helmi and coworkers, which we refer to as the H99 streams. These streams have a double-peaked velocity distribution in the z direction. We use the results of modeling of the H99 streams by Helmi and collaborators to test how one might use v_z velocity information and radial velocity information to detect kinematic substructure in the halo. We find that detecting the H99 streams with radial velocities alone would require a large sample. We use the velocity distribution of the H99 streams to estimate their age. From our model of the progenitor of the H99 streams, we determine that it was accreted between 6 and 9 Gyr ago. The H99 streams have [alpha/Fe] abundances similar to other halo stars in the solar neighborhood, suggesting that the gas that formed these stars were enriched mostly by Type II SNe. We have also discovered in angular momentum space two other possible substructures, which we refer to as the retrograde and prograde outliers. The retrograde outliers are likely to be halo substructure, but the prograde outliers are most likely part of the smooth halo. The retrograde outliers have significant structure in the v_phi direction and show a range of [alpha/Fe]. The methods presented in this paper can be used to exploit the kinematic information present in future large databases like RAVE, SDSSII/SEGUE, and Gaia.Comment: 46 pages, 13 figures, and 9 tables. Minor changes to text to match proofed version of the paper. Low resolution figures. High resolution version at http://www.astro.wisc.edu/~kepley/solar_streams.p

Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere

Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.NIH grants: (GM082989, CA186430, GM008275, GM008216, GM007229); American Heart Association predoctoral fellowship; American Cancer Society postdoctoral fellowship; NSF grant: (agreement DMR-0944772)

Differentiating criminal networks in the illegal wildlife trade: organized, corporate and disorganized crime

Historically, the poaching of wildlife was portrayed as a small-scale local activity in which only small numbers of wildlife would be smuggled illegally by collectors or opportunists. Nowadays, this image has changed: criminal networks are believed to be highly involved in wildlife trafficking, which has become a significant area of illicit activity. Even though wildlife trafficking has become accepted as a major area of crime and an important topic and criminologists have examined a variety of illegal wildlife markets, research that specifically focusses on the involvement of different criminal networks and their specific nature is lacking. The concept of a ‘criminal network’ or ‘serious organized crime’ is amorphous – getting used interchangeably and describes all crime that is structured rather than solely reflecting crime that fits within normative definitions of ‘organized’ crime. In reality, criminal networks are diverse. As such, we propose categories of criminal networks that are evidenced in the literature and within our own fieldwork: (1) organized crime groups (2) corporate crime groups and (3) disorganized criminal networks. Whereas there are instances when these groups act alone, this article will (also) discuss the overlap and interaction that occurs between our proposed categories and discuss the complicated nature of the involved criminal networks as well as predictions as to the future of these networks

An anatomy of Turkish football match-fixing

While discussion on corruption in sport is intensifying and football match-fixing in particular is attracting increasing attention, new fixing scandals emerge offering new accounts of actors and corrupt practices within the football industry and the level of the external threat to the sport. The scandal exposure of fixed matches in Turkey in 2011 sheds light on the fixing of 17 matches played in the 2010/11 football season and allowed for insights to the actors, structure and processes behind the fix. Following four criminal and seven disciplinary proceedings, the case is still pending appeal for its final decision, involving a total of 93 suspects and having already resulted in the exclusion of two teams from European competitions. The evidence collected by the authorities points towards a hierarchical criminal organisation led by the President of a football club that arranged and coordinated the fixing in order for his team to win the national Championship. The aim of this article is to provide an account of the organisation and coordination of match-fixing in Turkey, with its actors, specifics and criminal characteristics, while offering an examination of match-fixing for sporting success, the least documented type of match-fixing

An area of untapped potential? The use of restorative justice in the fight against serious and organized crime : a perception study

This article presents the results of a perception study which examined the potential for deploying restorative justice (RJ) in the context of serious and organized crime (SOC) offending. This is a hitherto unexplored area of debate and the study sought to engage the key stakeholders in RJ processes – victims, offenders and practitioners – to gather their views as to the suitability and desirability of extending RJ in this way. Employing a mixed methods approach, the study engaged over 40 participants across the three stakeholder groups. The findings challenge existing, deeply embedded orthodoxies concerning the very nature of SOC offending and offenders’ motivations, as well confirming the multiplicity of SOC victims’ expectations. The findings also demonstrate the urgent need for further debate concerning how best to account for the complexity of SOC victims’ needs which are currently unmet by the systemic limits of the criminal justice system

Two Structures of a Thiazolinyl Imine Reductase from Yersinia enterocolitica Provide Insight into Catalysis and Binding to the Nonribosomal Peptide Synthetase Module of HMWP1

The thiazolinyl imine reductase from Yersinia enterocolitica (Irp3) catalyzes the NADPH-dependent reduction of a thiazoline ring in an intermediate for the formation of the siderophore yersiniabactin. Two structures of Irp3 were determined in the apo- (1.85 Å) and NADP+-bound (2.31 Å) forms. Irp3 shows structural homology to sugar oxidoreductases such as glucose-fructose oxidoreductase and 1,5-anhydro-D-fructose reductase, as well as to biliverdin reductase. A homology model of the thiazolinyl imine reductase from Pseudomonas aeruginosa (PchG) was generated. Extensive loop insertions are observed in the C-terminal domain that are unique to Irp3 and PchG and not found in the structural homologs that recognize small molecular substrates. These loops are hypothesized to be important for binding of the nonribosomal peptide synthetase modules (found in HMWP1 and PchF, respectively) to which the substrate of the reductase is covalently attached. A catalytic mechanism of proton donation from a general acid (either histidine-101 or tyrosine-128) and hydride donation from C4 of nicotinamide of the NADPH cofactor is proposed for reduction of the carbon-nitrogen double bond of the thiazoline