bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and Scriptable Molecular Graphics in Web Browsers without Java3D
Authors: Willighagen Egon , Howard Miguel 
Published: June 2007

AbstractJmol is a free, open source molecule viewer for chemistry and biochemistry. It is cross-platform, running on Windows, Mac OS X, and Linux/Unix systems. The software consists of three parts: the JmolApplet is a web browser applet that can be integrated into web pages; the Jmol application is a standalone Java application that runs on the desktop; and the JmolViewer is a development tool kit that can be integrated into other Java applications.
Development of a bibliography on religion, spirituality and addictions
Authors: GEPPERT CYNTHIA , BOGENSCHUTZ MICHAEL P. , MILLER WILLIAM R. 
Published: June 2007

AbstractIntroduction and Aims. The aim of this study was to develop a comprehensive annotated public‐domain bibliography of the literature on spirituality and addictions to facilitate future research and scholarship. Design and Methods. A search was conducted of all citations listed in the MEDLINE, PsychINFO and ALTA Religion databases covering a period from 1941 to 2004 using the following search terms: substance abuse, substance dependence, addiction, religion, spirituality. A group of experts in the field then classified each citation according to empirically derived categories. Results. A total of 1353 papers met the search parameters and were classified into 10 non‐exclusive categories: (1) attitudes toward spirituality and substance use, (2) commentaries, (3) spiritual practices and development in recovery, (4) spiritual and religion variables in the epidemiology of substance abuse, (5) psychoactive substances and spiritual experiences, (6) religious and spiritual interventions, (7) literature reviews, (8) measurement of spirituality and addictions, (9) 12‐Step spirituality and (10) youth and development. Discussion and Conclusions. The literature is voluminous, but has focused primarily in a few areas. Common findings included an inverse relationship between religiosity and substance use/abuse, reduced use among those practising meditation and protective effects of 12‐Step group involvement during recovery. Although sound instruments are available for measuring spirituality, studies have tended to use simplistic, often single‐item measures. [Geppert C, Bogenschutz MP, Miller WR. Development of a bibliography on religion, spirituality and addictions. Drug Alcohol Rev 2007;26:389–395]
Evidence‐based policy or policy‐based evidence? The role of evidence in the development and implementation of the Illicit Drug Diversion Initiative
Authors: HUGHES CAITLIN E. 
Published: June 2007

AbstractIssues. Evidence‐based policy is promoted as the ideal in drug policy, yet public policy theorists suggest that policy‐based evidence may be a more fitting analogy, where evidence is used selectively to support a predetermined policy direction. Approach. The following paper assesses the resonance of this notion to the development of the Illicit Drug Diversion Initiative (IDDI), an apparently pragmatic reform adopted in Australia in 1999 through the Federal Coalition ‘Tough on Drugs’ strategy. It utilises interviews with key informants from the Australian drug policy arena conducted in 2005 to assess the role of evidence in the design and implementation of the IDDI. Key Findings. The current paper shows that while policy‐makers were generally supportive of the IDDI and viewed drug diversion as a more pragmatic response to drug users, they contend that implementation has suffered through a selective and variable emphasis upon evidence. Most notably, the IDDI is not premised upon best‐practice objectives of reducing harm from drug use, but instead on ‘Tough on Drugs’ objectives of reducing drug use and crime. Implications. This paper contends that policy‐based evidence may facilitate the adoption of pragmatic reforms, but reduce the capacity for effective reform. It therefore has both functional and dysfunctional elements. Conclusion. The paper concludes that greater attention is needed to understanding how to mesh political and pragmatic objectives, and hence to maximise the benefits from policy‐based evidence. [Hughes CE. Evidence‐based policy or policy‐based evidence? The role of evidence in the development and implementation of the Illicit Drug Diversion Initiative. Drug Alcohol Rev 2007;26:363–368]
Adolescent use of illicit drugs and adult offending: a Swedish longitudinal study
Authors: STENBACKA MARLENE , STATTIN HÅKAN 
Published: June 2007

AbstractThe main aim of this study was to examine the role of illicit drug use before the age of 18 years in developing a criminal career. The study included 7577 18‐year‐old men conscripted for military service in Stockholm County in 1969/1970. At enrolment they answered questions regarding alcohol and illicit drug use, social background, behavioural factors and health. Data on adult and adolescent criminality were obtained from official registers from the age of 15 to the age of 43. Subjects with self‐reported drug use were registered significantly more often (p ≤ 0.0001) for future drug offences and other non‐drug offences than were subjects with no drug use at all. Irrespective of the number of adolescent offences, if subjects also reported illicit drug use in adolescence, their adult criminal activity was considerably higher than if they had not used any drugs during adolescence. This was also true when examining other risk factors. Generally, adolescent illicit drug use was a risk factor over and above common risk factors for adult criminality. Early prevention of illicit substance use and criminality in adolescence is important in hindering a future criminal career. [Stenbacka M, Stattin H. Adolescent use of illicit drugs and adult offending: a Swedish longitudinal study. Drug Alcohol Rev 2007;26:397–403]
The costs and consequences of three policy options for reducing heroin dependency
Authors: MOORE TIMOTHY J. , RITTER ALISON , CAULKINS JONATHAN P. 
Published: June 2007

AbstractIntroduction and Aims. This study compares the costs and consequences of three interventions for reducing heroin dependency: pharmacotherapy maintenance, residential rehabilitation and prison. Design and Methods. Using Australian data, the interventions' cost‐consequence ratio was estimated, taking into consideration reduction in heroin use during the intervention; the length of intervention; and post‐intervention effects (as measured by abstinence rates). Sensitivity analyses were conducted, including varying the magnitude and duration of treatment effects, and ascribing positive outcomes only to treatment completers. A hybrid model that combined pharmacotherapy maintenance with a prison term was also considered. Results. If the post‐programme abstinence rates are sustained for 2 years, then for an average heroin user the cost of averting a year of heroin use is approximately AUD$5000 for pharmacotherapy maintenance, AUD$11 000 for residential rehabilitation and AUD$52 000 for prison. Varying the parameters does not change the ranking of the programmes. If the completion rate in pharmacotherapy maintenance was raised above 95% (by the threat of prison for non‐completers), the combined model of treatment plus prison may become the most cost‐effective option. Discussion and Conclusions. Relative performance in terms of costs and consequences is an important consideration in the policy decision‐making process, and quantitative data such as those reported herein can provide insights pertinent to evidence‐based policy. [Moore TJ, Ritter A, Caulkins JP. The costs and consequences of three policy options for reducing heroin dependency. Drug Alcohol Rev 2007;26:369–378]
Hepatitis B immunity in a population of drug and alcohol users
Authors: POLIZZOTTO M. N. , WHELAN G. 
Published: June 2007

AbstractThe objective of this study was to determine the level of immunity from Hepatitis B infection in an Australian population of drug and alcohol users, and the validity of self‐reported immune status. A cross‐sectional survey was employed of drug and alcohol users presenting for treatment, who were clients of De Paul House, a community‐based drug and alcohol withdrawal service in Victoria. Outcome measures were: hepatitis B serology and personal reports of hepatitis B immunity. A total of 118 people were enrolled; 22% were injecting drug users and 48% reported past injecting drug use, while 55% were alcohol users; 51% had no general practitioner; 73% of participants were unaware of whether they were protected from hepatitis B infection, while 19.5% believed they were protected. However, serology demonstrated that 52.2% of those who believed they were protected were not immune. Only 21% of participants were immune. This is the first study in an Australian setting since the 1970s to examine the effectiveness of vaccination targeted to this population, and demonstrates low rates of immunity. New strategies are needed to deliver vaccination to this group. These will need to take account of the often chaotic nature of their lives, the poor validity of self‐reported immunity, and the lack of primary care links. [Polizzotto MN, Whelan G. Hepatitis B immunity in a population of drug and alcohol users. Drug Alcohol Rev 2007;26:417–419]
Boltzmann probability of RNA structural neighbors and riboswitch detection
Authors: Freyhult Eva , Moulton Vincent , Clote Peter 
Published: June 2007

Abstract
Motivation: We describe algorithms implemented in a new software package, RNAbor, to investigate structures in a neighborhood of an input secondary structure S of an RNA sequence s. The input structure could be the minimum free energy structure, the secondary structure obtained by analysis of the X-ray structure or by comparative sequence analysis, or an arbitrary intermediate structure.
Results: A secondary structure T of s is called a δ-neighbor of S if T and S differ by exactly δ base pairs. RNAbor computes the number (Nδ), the Boltzmann partition function (Zδ) and the minimum free energy (MFEδ) and corresponding structure over the collection of all δ-neighbors of S. This computation is done simultaneously for all δ ≤ m, in run time O (mn3) and memory O(mn2), where n is the sequence length. We apply RNAbor for the detection of possible RNA conformational switches, and compare RNAbor with the switch detection method paRNAss. We also provide examples of how RNAbor can at times improve the accuracy of secondary structure prediction.
Availability: http://bioinformatics.bc.edu/clotelab/RNAbor/
Contact: clote@bc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Threading a peptide through a peptide: Protein loops, rotaxanes, and knots
Authors: Blankenship John W. , Dawson Philip E. 
Published: June 2007

AbstractProteins adopt complex folds in nature that typically avoid conformations that are knotted or “threaded” through closed loops. Is this the result of fundamental barriers to folding, or have proteins simply evolved to avoid threaded conformations? Organic synthesis has been used in supramolecular chemistry to install topological links in small molecules. By following these principles, we now show that it is possible to assemble a topologically linked protein complex by threading a linear protein through a cyclic protein to form a [2]pseudo‐rotaxane. Subsequent ring closure using native chemical ligation cyclizes the linear protein, forming a [2]heterocatenane. Although the kinetics of protein threading are slower than the folding kinetics of the native protein, threading appears to be a highly efficient process.
Kinetic and structural analysis of a bacterial protein tyrosine phosphatase‐like myo‐inositol polyphosphatase
Authors: Puhl Aaron A. , Gruninger Robert J. , Greiner Ralf , Janzen Timothy W. , Mosimann Steven C. , Selinger L. Brent 
Published: June 2007

AbstractPhyA from Selenomonas ruminantium (PhyAsr), is a bacterial protein tyrosine phosphatase (PTP)‐like inositol polyphosphate phosphatase (IPPase) that is distantly related to known PTPs. PhyAsr has a second substrate binding site referred to as a standby site and the P‐loop (HCX5R) has been observed in both open (inactive) and closed (active) conformations. Site‐directed mutagenesis and kinetic and structural studies indicate PhyAsr follows a classical PTP mechanism of hydrolysis and has a broad specificity toward polyphosphorylated myo‐inositol substrates, including phosphoinositides. Kinetic and molecular docking experiments demonstrate PhyAsr preferentially cleaves the 3‐phosphate position of Ins P6 and will produce Ins(2)P via a highly ordered series of sequential dephosphorylations: D‐Ins(1,2,4,5,6)P5, Ins(2,4,5,6)P4, D‐Ins(2,4,5)P3, and D‐Ins(2,4)P2. The data support a distributive enzyme mechanism and suggest the PhyAsr standby site is involved in the recruitment of substrate. Structural studies at physiological pH and high salt concentrations demonstrate the “closed” or active P‐loop conformation can be induced in the absence of substrate. These results suggest PhyAsr should be reclassified as a D‐3 myo‐inositol hexakisphosphate phosphohydrolase and suggest the PhyAsr reaction mechanism is more similar to that of PTPs than previously suspected.
A high‐throughput method for membrane protein solubility screening: The ultracentrifugation dispersity sedimentation assay
Authors: Gutmann Daniel A.P. , Mizohata Eiichi , Newstead Simon , Ferrandon Sebastian , Henderson Peter J.F. , van Veen Hendrik W. , Byrne Bernadette 
Published: June 2007

AbstractOne key to successful crystallization of membrane proteins is the identification of detergents that maintain the protein in a soluble, monodispersed state. Because of their hydrophobic nature, membrane proteins are particularly prone to forming insoluble aggregates over time. This nonspecific aggregation of the molecules reduces the likelihood of the regular association of the protein molecules essential for crystal lattice formation. Critical buffer components affecting the aggregation of membrane proteins include detergent choice, salt concentration, and presence of glycerol. The optimization of these parameters is often a time‐ and protein‐consuming process. Here we describe a novel ultracentrifugation dispersity sedimentation (UDS) assay in which ultracentrifugation of very small (5 μL) volumes of purified, soluble membrane protein is combined with SDS‐PAGE analysis to rapidly assess the degree of protein aggregation. The results from the UDS method correlate very well with established methods like size‐exclusion chromatography (SEC), while consuming considerably less protein. In addition, the UDS method allows rapid screening of detergents for membrane protein crystallization in a fraction of the time required by SEC. Here we use the UDS method in the identification of suitable detergents and buffer compositions for the crystallization of three recombinant prokaryotic membrane proteins. The implications of our results for membrane protein crystallization prescreening are discussed.
An artificially evolved albumin binding module facilitates chemical shift epitope mapping of GA domain interactions with phylogenetically diverse albumins
Authors: He Yanan , Chen Yihong , Rozak David A. , Bryan Philip N. , Orban John 
Published: June 2007

AbstractProtein G‐related albumin‐binding (GA) modules occur on the surface of numerous Gram‐positive bacterial pathogens and their presence may promote bacterial growth and virulence in mammalian hosts. We recently used phage display selection to evolve a GA domain, PSD‐1 (phage selected domain‐1), which tightly bound phylogenetically diverse albumins. With respect to PSD‐1's broad albumin binding specificity, it remained unclear how the evolved binding epitope compared to those of naturally occurring GA domains and whether PSD‐1's binding mode was the same for different albumins. We investigate these questions here using chemical shift perturbation measurements of PSD‐1 with rabbit serum albumin (RSA) and human serum albumin (HSA) and put the results in the context of previous work on structure and dynamics of GA domains. Combined, these data provide insights into the requirements for broad binding specificity in GA‐albumin interactions. Moreover, we note that using the phage‐optimized PSD‐1 protein significantly diminishes the effects of exchange broadening at the binding interface between GA modules and albumin, presumably through stabilization of a ligand‐bound conformation. The employment of artificially evolved domains may be generally useful in NMR structural studies of other protein–protein complexes.
Functional structure of the somatomedin B domain of vitronectin
Authors: Zhou Aiwu 
Published: June 2007

AbstractThe N‐terminal somatomedin B domain (SMB) of vitronectin binds PAI‐1 and the urokinase receptor with high affinity and regulates tumor cell adhesion and migration. We have shown previously in the crystal structure of the PAI‐1/SMB complex that SMB, a peptide of 51 residues, is folded as a compact cysteine knot of four pairs of crossed disulfide bonds. However, the physiological significance of this structure was questioned by other groups, who disputed the disulfide bonding shown in the crystal structure (Cys5–Cys21, Cys9–Cys39, Cys19–Cys32, Cys25–Cys31), notably claiming that the first disulfide is Cys5–Cys9 rather than the Cys5–Cys21 bonding shown in the structure. To test if the claimed Cys5–Cys9 bond does exist in the SMB domain of plasma vitronectin, we purified mouse and rat plasma vitronectin that have a Met (hence cleavable by cyanogen bromide) at residue 14, and also prepared recombinant human SMB variants from insect cells with residues Asn14 or Leu24 mutated to Met. HPLC and mass spectrometry analysis showed that, after cyanogen bromide digestion, all the fragments of the SMB derived from mouse or rat vitronectin or the recombinant SMB mutants are still linked together by disulfides, and the N‐terminal peptide (residue 1–14 or 1–24) can only be released when the disulfide bonds are broken. This clearly demonstrates that Cys5 and Cys9 of SMB do not form a disulfide bond in vivo, and together with other structural evidence confirms that the only functional structure of the SMB domain of plasma vitronectin is that seen in its crystallographic complex with PAI‐1.
Chemical cross‐linking of the chloroplast localized small heat‐shock protein, Hsp21, and the model substrate citrate synthase
Authors: Åhrman Emma , Lambert Wietske , Aquilina J. Andrew , Robinson Carol V. , Emanuelsson Cecilia Sundby 
Published: June 2007

AbstractThe molecular mechanism whereby the small heat‐shock protein (sHsp) chaperones interact with and prevent aggregation of other proteins is not fully understood. We have characterized the sHsp–substrate protein interaction at normal and increased temperatures utilizing a model substrate protein, citrate synthase (CS), widely used in chaperone assays, and a dodecameric plant sHsp, Hsp21, by chemical cross‐linking with 3,3′‐Dithiobis[sulfosuccinimidylpropionate] (DTSSP) and mass spectrometric peptide mapping. In the absence of CS, the cross‐linker captured Hsp21 in dodecameric form, even at increased temperature (47°C). In the presence of equimolar amounts of CS, no Hsp21 dodecamer was captured, indicating a substrate‐induced Hsp21 dodecamer dissociation by equimolar amounts of CS. Cross‐linked Hsp21–Hsp21 dipeptides indicated an exposure of the Hsp21 C‐terminal tails and substrate‐binding sites normally covered by the C terminus. Cross‐linked Hsp21–CS dipeptides mapped to several sites on the surface of the CS dimer, indicating that there are numerous weak and short‐lived interactions between Hsp21 and CS, even at normal temperatures. The N‐terminal arms especially interacted with a motif in the CS dimer, which is absent in thermostable forms of CS. The cross‐linking data suggest that the presence of substrate rather than temperature influences the conformation of Hsp21.
Solution structure of a membrane‐anchored ubiquitin‐fold (MUB) protein from Homo sapiens
Authors: de la Cruz Norberto B. , Peterson Francis C. , Lytle Betsy L. , Volkman Brian F. 
Published: June 2007

AbstractThe protein Bc059385, whose solution structure is reported here, is the human representative of a recently identified family of membrane‐anchored ubiquitin‐fold (MUB) proteins. Analysis of their similarity to ubiquitin indicates that homologous amino acid residues in MUBs form a hydrophobic surface very similar to the recognition patch surrounding Ile‐44 in ubiquitin. This suggests that MUBs may interact with proteins containing an α‐helical motif similar to those of some ubiquitin binding domains. A disordered loop common to MUBs may also provide a second protein interaction site. From the available data, it is probable that this protein is prenylated and associated with the membrane. With <20% identity to ubiquitin, the MUB family further expands the sequence space that maps to the β‐grasp fold, and adds membrane localization to its list of functional roles.
Active site geometry of glucose‐1‐phosphate uridylyltransferase
Authors: Thoden James B. , Holden Hazel M. 
Published: June 2007

AbstractGlucose‐1‐phosphate uridylyltransferase, or UGPase, catalyzes the production of UDP‐glucose from glucose‐1‐phosphate and UTP. Because of the biological role of UDP‐glucose in glycogen synthesis and in the formation of glycolipids, glycoproteins, and proteoglycans, the enzyme is widespread in nature. Recently this laboratory reported the three‐dimensional structure of UGPase from Escherichia coli. While the initial X‐ray analysis revealed the overall fold of the enzyme, details concerning its active site geometry were limited because crystals of the protein complexed with either substrates or products could never be obtained. In an effort to more fully investigate the active site geometry of the enzyme, UGPase from Corynebacterium glutamicum was subsequently cloned and purified. Here we report the X‐ray structure of UGPase crystallized in the presence of both magnesium and UDP‐glucose. Residues involved in anchoring the ligand to the active site include the polypeptide chain backbone atoms of Ala 20, Gly 21, Gly 117, Gly 180, and Ala 214, and the side chains of Glu 36, Gln 112, Asp 143, Glu 201, and Lys 202. Two magnesium ions are observed coordinated to the UDP‐glucose. An α‐ and a β‐phosphoryl oxygen, three waters, and the side chain of Asp 142 ligate the first magnesium, whereas the second ion is coordinated by an α‐phosphoryl oxygen and five waters. The position of the first magnesium is conserved in both the glucose‐1‐phosphate thymidylyltransferases and the cytidylyltransferases. The structure presented here provides further support for the role of the conserved magnesium ion in the catalytic mechanisms of the sugar‐1‐phosphate nucleotidylyltransferases.