bluuebunny/crossref_metadata_2025 huggingface dataset:
Raised Without Antibiotics: Lessons from Voluntary Labeling of Antibiotic Use Practices in The Broiler Industry
Authors: Bowman Maria , Marshall Kandice K. , Kuchler Fred , Lynch Lori
Published: March 2016

Voluntary labeling improves market efficiency if consumers receive the product characteristics they demand and producers are compensated for producing these characteristics. For this to occur, label claims have to be truthful, credible, and understandable. We examine the introduction of “Raised Without Antibiotics” (RWA) label claims in the broiler industry by Perdue Farms (Perdue) and Tyson Foods (Tyson) in 2007 and the events that follow. We ask whether voluntary label claims were able to improve efficiency in the market for RWA chicken products. In this case, evidence presented as part of court testimony suggests that Tyson did not deliver the RWA attribute that consumers demanded, competitors suffered, and Tyson profited from introducing what was ruled to be a false and misleading label claim to the marketplace. While the media informed consumers and stockholders of these events, we found little evidence in publicly available data, literature, or documentation from court cases that Tyson suffered significant harm in the market, or from stockholders. The U.S. Department of Agriculture Food Safety and Inspection Service did ultimately remove Tyson's label claims from the marketplace, and the legal system provided some redress to competitors and consumers. Even so, labels with animal raising claims (such as RWA) and voluntary, process‐based label claims (in general) continue to be challenged by similar issues, that is, consumer confusion, the absence of universally accepted definitions, and varying degrees of credibility.
pileup.js: a JavaScript library for interactive and in-browser visualization of genomic data
Authors: Vanderkam Dan , Aksoy B. Arman , Hodes Isaac , Perrone Jaclyn , Hammerbacher Jeff
Published: March 2016

pileup.js is a new browser-based genome viewer. It is designed to facilitate the investigation of evidence for genomic variants within larger web applications. It takes advantage of recent developments in the JavaScript ecosystem to provide a modular, reliable and easily embedded library.

Availability and implementation: The code and documentation for pileup.js is publicly available at https://github.com/hammerlab/pileup.js under the Apache 2.0 license.

Contact: correspondence@hammerlab.org
Analysis of clinical decision support system malfunctions: a case series and survey
Authors: Wright Adam , Hickman Thu-Trang T , McEvoy Dustin , Aaron Skye , Ai Angela , Andersen Jan Marie , Hussain Salman , Ramoni Rachel , Fiskio Julie , Sittig Dean F , Bates David W
Published: March 2016

Objective To illustrate ways in which clinical decision support systems (CDSSs) malfunction and identify patterns of such malfunctions.

Materials and Methods We identified and investigated several CDSS malfunctions at Brigham and Women’s Hospital and present them as a case series. We also conducted a preliminary survey of Chief Medical Information Officers to assess the frequency of such malfunctions.

Results We identified four CDSS malfunctions at Brigham and Women’s Hospital: (1) an alert for monitoring thyroid function in patients receiving amiodarone stopped working when an internal identifier for amiodarone was changed in another system; (2) an alert for lead screening for children stopped working when the rule was inadvertently edited; (3) a software upgrade of the electronic health record software caused numerous spurious alerts to fire; and (4) a malfunction in an external drug classification system caused an alert to inappropriately suggest antiplatelet drugs, such as aspirin, for patients already taking one. We found that 93% of the Chief Medical Information Officers who responded to our survey had experienced at least one CDSS malfunction, and two-thirds experienced malfunctions at least annually.

Discussion CDSS malfunctions are widespread and often persist for long periods. The failure of alerts to fire is particularly difficult to detect. A range of causes, including changes in codes and fields, software upgrades, inadvertent disabling or editing of rules, and malfunctions of external systems commonly contribute to CDSS malfunctions, and current approaches for preventing and detecting such malfunctions are inadequate.

Conclusion CDSS malfunctions occur commonly and often go undetected. Better methods are needed to prevent and detect these malfunctions.
IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples
Authors: Hintzsche Jennifer , Kim Jihye , Yadav Vinod , Amato Carol , Robinson Steven E , Seelenfreund Eric , Shellman Yiqun , Wisell Joshua , Applegate Allison , McCarter Martin , Box Neil , Tentler John , De Subhajyoti , Robinson William A , Tan Aik Choon
Published: March 2016

Objective Currently, there is a disconnect between finding a patient’s relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics.

Methods and materials The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment.

Results IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies.

Conclusion IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine.

IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT.
Enteric disease episodes and the risk of acquiring a future sexually transmitted infection: a prediction model in Montreal residents
Authors: Caron Melissa , Allard Robert , Bédard Lucie , Latreille Jérôme , Buckeridge David L
Published: March 2016

Objective. The sexual transmission of enteric diseases poses an important public health challenge. We aimed to build a prediction model capable of identifying individuals with a reported enteric disease who could be at risk of acquiring future sexually transmitted infections (STIs).

Materials and Methods. Passive surveillance data on Montreal residents with at least 1 enteric disease report was used to construct the prediction model. Cases were defined as all subjects with at least 1 STI report following their initial enteric disease episode. A final logistic regression prediction model was chosen using forward stepwise selection.

Results. The prediction model with the greatest validity included age, sex, residential location, number of STI episodes experienced prior to the first enteric disease episode, type of enteric disease acquired, and an interaction term between age and male sex. This model had an area under the curve of 0.77 and had acceptable calibration.

Discussion. A coordinated public health response to the sexual transmission of enteric diseases requires that a distinction be made between cases of enteric diseases transmitted through sexual activity from those transmitted through contaminated food or water. A prediction model can aid public health officials in identifying individuals who may have a higher risk of sexually acquiring a reportable disease. Once identified, these individuals could receive specialized intervention to prevent future infection.

Conclusion. The information produced from a prediction model capable of identifying higher risk individuals can be used to guide efforts in investigating and controlling reported cases of enteric diseases and STIs.
Female dietary bias towards large migratory moths in the European free-tailed bat (
Tadarida teniotis
)
Authors: Mata Vanessa A. , Amorim Francisco , Corley Martin F. V. , McCracken Gary F. , Rebelo Hugo , Beja Pedro
Published: March 2016

In bats, sexual segregation has been described in relation to differential use of roosting and foraging habitats. It is possible that variation may also exist between genders in the use of different prey types. However, until recently this idea was difficult to test owing to poorly resolved taxonomy of dietary studies. Here, we use high-throughput sequencing to describe gender-related variation in diet composition of the European free-tailed bat (
Tadarida teniotis
), while controlling for effects of age and season. We analysed guano pellets collected from 143 individuals mist-netted from April to October 2012 and 2013, in northeast Portugal. Moths (Lepidoptera; mainly Noctuidae and Geometridae) were by far the most frequently recorded prey, occurring in nearly all samples and accounting for 96 out of 115 prey taxa. There were significant dietary differences between males and females, irrespective of age and season. Compared to males, females tended to consume larger moths and more moths of migratory behaviour (e.g.
Autographa gamma
). Our study provides the first example of gender-related dietary variation in bats, illustrating the value of novel molecular tools for revealing intraspecific variation in food resource use in bats and other insectivores.
Migratory common blackbirds have lower innate immune function during autumn migration than resident conspecifics
Authors: Eikenaar Cas , Hegemann Arne
Published: March 2016

Animals need a well-functioning immune system to protect themselves against pathogens. The immune system, however, is costly and resource trade-offs with other demands exist. For migratory animals several (not mutually exclusive) hypotheses exist. First, migrants reduce immune function to be able to allocate resources to migration. Second, migrants boost immune function to cope with more and/or novel pathogens encountered during migration. Third, migrants reallocate resources within the immune system. We tested these hypotheses by comparing baseline immune function in resident and migratory common blackbirds (
Turdus merula
), both caught during the autumn migration season on the island of Helgoland, Germany. Indices of baseline innate immune function (microbial killing capacity and haptoglobin-like activity) were lower in migrants than in residents. There was no difference between the groups in total immunoglobulins, a measure of baseline acquired immune function. Our study on a short-distance avian migrant supports the hypothesis that innate immune function is compromised during migration.
Insect–computer hybrid legged robot with user-adjustable speed, step length and walking gait
Authors: Cao Feng , Zhang Chao , Choo Hao Yu , Sato Hirotaka
Published: March 2016

We have constructed an insect–computer hybrid legged robot using a living beetle (Mecynorrhina torquata; Coleoptera). The protraction/retraction and levation/depression motions in both forelegs of the beetle were elicited by electrically stimulating eight corresponding leg muscles via eight pairs of implanted electrodes. To perform a defined walking gait (e.g. gallop), different muscles were individually stimulated in a predefined sequence using a microcontroller. Different walking gaits were performed by reordering the applied stimulation signals (i.e. applying different sequences). By varying the duration of the stimulation sequences, we successfully controlled the step frequency and hence the beetle's walking speed. To the best of our knowledge, this paper presents the first demonstration of living insect locomotion control with a user-adjustable walking gait, step length and walking speed.
Neutral glycans from sandfish skin can reduce friction of polymers
Authors: Vihar Boštjan , Hanisch Franz Georg , Baumgartner Werner
Published: March 2016

The lizard
Scincus scincus
, also known as sandfish, can move through aeolian desert sand in a swimming-like manner. A prerequisite for this ability is a special integument, i.e. scales with a very low friction for sand and a high abrasion resistance. Glycans in the scales are causally related to the low friction. Here, we analysed the glycans and found that neutral glycans with five to nine mannose residues are important. If these glycans were covalently bound to acrylic polymers like poly(methyl methacrylate) or acrylic car coatings at a density of approximately one molecule per 4 nm², friction for and adhesion of sand particles could be reduced to levels close to those observed with sandfish scales. This was also found true, if the glycans were isolated from sources other than sandfish scales like plants such as almonds or mistletoe. We speculate that these neutral glycans act as low density spacers separating sand particles from the dense scales thereby reducing van der Waals forces.
Heparin binding preference and structures in the fibroblast growth factor family parallel their evolutionary diversification
Authors: Li Yong , Sun Changye , Yates Edwin A. , Jiang Chao , Wilkinson Mark C. , Fernig David G.
Published: March 2016

The interaction of a large number of extracellular proteins with heparan sulfate (HS) regulates their transport and effector functions, but the degree of molecular specificity underlying protein–polysaccharide binding is still debated. The 15 paracrine fibroblast growth factors (FGFs) are one of the paradigms for this interaction. Here, we measure the binding preferences of six FGFs (FGF3, FGF4, FGF6, FGF10, FGF17, FGF20) for a library of modified heparins, representing structures in HS, and model glycosaminoglycans, using differential scanning fluorimetry. This is complemented by the identification of the lysine residues in the primary and secondary binding sites of the FGFs by a selective labelling approach. Pooling these data with previous sets provides good coverage of the FGF phylogenetic tree, deduced from amino acid sequence alignment. This demonstrates that the selectivity of the FGFs for binding structures in sulfated polysaccharides and the pattern of secondary binding sites on the surface of FGFs follow the phylogenetic relationship of the FGFs, and so are likely to be the result of the natural selection pressures that led to the expansion of the FGF family in the course of the evolution of more complex animal body plans.
Temporal and phylogenetic evolution of the sauropod dinosaur body plan
Authors: Bates Karl T. , Mannion Philip D. , Falkingham Peter L. , Brusatte Stephen L. , Hutchinson John R. , Otero Alejandro , Sellers William I. , Sullivan Corwin , Stevens Kent A. , Allen Vivian
Published: March 2016

The colossal size and body plan of sauropod dinosaurs are unparalleled in terrestrial vertebrates. However, to date, there have been only limited attempts to examine temporal and phylogenetic patterns in the sauropod bauplan. Here, we combine three-dimensional computational models with phylogenetic reconstructions to quantify the evolution of whole-body shape and body segment properties across the sauropod radiation. Limitations associated with the absence of soft tissue preservation in fossils result in large error bars about mean absolute body shape predictions. However, applying any consistent skeleton : body volume ratio to all taxa does yield changes in body shape that appear concurrent with major macroevolutionary events in sauropod history. A caudad shift in centre-of-mass (CoM) in Middle Triassic Saurischia, associated with the evolution of bipedalism in various dinosaur lineages, was reversed in Late Triassic sauropodomorphs. A craniad CoM shift coincided with the evolution of quadrupedalism in the Late Triassic, followed by a more striking craniad shift in Late Jurassic–Cretaceous titanosauriforms, which included the largest sauropods. These craniad CoM shifts are strongly correlated with neck enlargement, a key innovation in sauropod evolution and pivotal to their gigantism. By creating a much larger feeding envelope, neck elongation is thought to have increased feeding efficiency and opened up trophic niches that were inaccessible to other herbivores. However, we find that relative neck size and CoM position are not strongly correlated with inferred feeding habits. Instead the craniad CoM positions of titanosauriforms appear closely linked with locomotion and environmental distributions, potentially contributing to the continued success of this group until the end-Cretaceous, with all other sauropods having gone extinct by the early Late Cretaceous.
Variation in relapse frequency and the transmission potential of
Plasmodium vivax
malaria
Authors: White Michael T. , Shirreff George , Karl Stephan , Ghani Azra C. , Mueller Ivo
Published: March 2016

There is substantial variation in the relapse frequency of
Plasmodium vivax
malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in
P. vivax
relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of
P. vivax
transmission and calculate the basic reproduction number
R
0
to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.
The dynamic landscape of fission yeast meiosis alternative-splice isoforms
Authors: Kuang Zheng , Boeke Jef D. , Canzar Stefan
Published: March 2016

Alternative splicing increases the diversity of transcriptomes and proteomes in metazoans. The extent to which alternative splicing is active and functional in unicellular organisms is less understood. Here we exploit a single-molecule long-read sequencing technique and develop an open-source software program called SpliceHunter, to characterize the transcriptome in the meiosis of fission yeast. We reveal 17017 alternative splicing events in 19741 novel isoforms at different stages of meiosis, including antisense and read-through transcripts. Intron retention is the major type of alternative splicing, followed by “alternate intron in exon”. 887 novel transcription units are detected; 60 of the predicted proteins show homology in other species and form theoretical stable structures. We compare the dynamics of novel isoforms based on the number of supporting full-length reads with those of annotated isoforms and explore the translational capacity and quality of novel isoforms. The evaluation of these factors indicates that the majority of novel isoforms are unlikely to be both condition-specific and translatable but the possibility of functional novel isoforms is not excluded. Moreover, the co-option of these unusual transcripts into newly born genes seems likely. Together, this study highlights the diversity and dynamics at the isoform level in the sexual development of fission yeast.
Genome-wide measurement of spatial expression in patterning mutants ofDrosophila melanogaster
Authors: Combs Peter A. , Eisen Michael B.
Published: March 2016

Genome sequencing has become commonplace, but the understanding of how those genomes ultimately specify cell fate during development is still elusive. Extrapolating insights from deep investigation of a handful of developmentally important Drosophila genes to understanding the regulation of all genes is a major challenge. The developing embryo provides a unique opportunity to study the role of gene expression in pattern specification; the precise and consistent spatial positioning of key transcription factors essentially provides separate transcriptional-readout experiments at a critical point in development.

We cryosectioned and sequenced mRNA from single Drosophila melanogaster embryos at the blastoderm stage to screen for spatially-varying regulation of transcription. Expanding on our previous screening of wild type embryos, here we present data from dosage mutants for key maternally provided regulators, including depletion of zelda and hunchback and both over-expression and depletion of bicoid. These data recapitulate all of the expected patterning changes driven by these regulators; for instance, we show spatially-confined up-regulation of expression in the bicoid over-expression condition, and down-regulation of those genes in the bicoid knock-down case, consistent with bicoid’s known function as an anterior-localized activator.

Our data highlight the role of combinatorial regulation of patterning gene expression. When comparing changes in multiple conditions, genes responsive to one mutation tend to respond to other mutations in a similar fashion. Furthermore, genes that respond differently to these mutations tend to have more complex patterns of TF binding.
SAMSA: A comprehensive metatranscriptome analysis pipeline
Authors: Westreich Samuel T , Korf Ian , Mills David A. , Lemay Danielle G
Published: March 2016

Background

Although metatranscriptomics—the study of diverse microbial population activity based on RNA-seq data—is rapidly growing in popularity, there are limited options for biologists to analyze this type of data. Current approaches for processing metatranscriptomes rely on restricted databases and a dedicated computing cluster, or metagenome-based approaches that have not been fully evaluated for processing metatranscriptomic datasets. We created a new bioinformatics pipeline, SAMSA, designed specifically for metatranscriptome dataset analysis, which runs either inhouse or in conjunction with Metagenome-RAST (MG-RAST) servers. Designed for use by researchers with relatively little bioinformatics experience, SAMSA offers a breakdown of metatranscriptome activity by organism or transcript function, and is fully open source. We next used this new tool to evaluate best practices for sequencing stool metatranscriptomes.

Results

Working with the MG-RAST annotation server, we constructed the Simple Annotation of Metatranscriptomes by Sequence Analysis (SAMSA) software package, a complete pipeline for the analysis of gut microbiome data. In creating this package, we determined optimal parameters in data collection and processing. SAMSA can summarize and evaluate raw annotation results, identifying abundant species and significant functional differences between metatranscriptomes.

Using pilot data and simulated subsets, we determined experimental requirements for fecal gut metatranscriptomes. Sequences need to be either long reads (longer than 100bp) or paired-end reads that can be joined. Each sample nees 40-50 million raw sequences which can be expected to yield the 5-10 million annotated reads necessary for accurate abundance measures. We also demonstrated that ribosomal RNA depletion does not equally deplete ribosomes from all species within a sample, and remaining rRNA sequences should be discarded. Using publicly available metatranscriptome data in which rRNA was not depleted, we were able to demonstrate that organism activity can be measured using mRNA counts. We were also able to detect significant differences between control and experimental groups in both organism activity and functional activity.

Conclusions

By making this new pipeline publicly available, we have created a powerful new tool for metatranscriptomics research, offering a new method for greater insight into the activity of diverse microbial communities. We further recommend that stool metatranscriptomes be ribodepleted and sequenced in a 100bp paired end format with a minimum of 40 million reads per sample.
Six polycyclic pyrimidoazepine derivatives: syntheses, molecular structures and supramolecular assembly
Authors: Acosta Quintero Lina M. , Palma Alirio , Cobo Justo , Glidewell Christopher
Published: March 2016

A versatile synthetic method has been developed for the formation of variously substituted polycyclic pyrimidoazepine derivatives, formed by nucleophilic substitution reactions on the corresponding chloro-substituted compounds; the reactions can be promoted either by conventional heating in basic solutions or by microwave heating in solvent-free systems. Thus, (6RS)-6,11-dimethyl-3,5,6,11-tetrahydro-4H-benzo[b]pyrimido[5,4-f]azepin-4-one, C14H15N3O, (I), was isolated from a solution containing (6RS)-4-chloro-8-hydroxy-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine and benzene-1,2-diamine; (6RS)-4-butoxy-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin-8-ol, C18H23N3O2, (II), was formed by reaction of the corresponding 6-chloro compound with butanol, and (RS)-4-dimethylamino-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin-8-ol, C16H20N4O, (III), was formed by reaction of the chloro analogue with alkaline dimethylformamide. (6RS)-N-Benzyl-8-methoxy-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepin-4-amine, C22H24N4O, (IV), (6RS)-N-benzyl-6-methyl-1,2,6,7-tetrahydropyrimido[5′,4′:6,7]azepino[3,2,1-hi]indol-8-amine, C22H22N4, (V), and (7RS)-N-benzyl-7-methyl-2,3,7,8-tetrahydro-1H-pyrimido[5′,4′:6,7]azepino[3,2,1-ij]quinolin-9-amine, C23H24N4, (VI), were all formed by reaction of the corresponding chloro compounds with benzylamine under microwave irradiation. In each of compounds (I)–(IV) and (VI), the azepine ring adopts a conformation close to the boat form, with the C-methyl group in a quasi-equatorial site, whereas the corresponding ring in (V) adopts a conformation intermediate between the twist-boat and twist-chair forms, with the C-methyl group in a quasi-axial site. No two of the structures of (I)–(VI) exhibit the same range of intermolecular hydrogen bonds: different types of sheet are formed in each of (I), (II), (V) and (VI), and different types of chain in each of (III) and (IV).
A three-dimensional mixed-valence CuII/CuIcoordination polymer constructed from biphenyl-3,4′,5-tricarboxylate and 1,4-bis(1H-imidazol-1-yl)benzene ligands
Authors: Liu Ya-Hui , Lu Li-Ping , Zhu Miao-Li , Su Feng
Published: March 2016

Coordination polymers (CPs) built by coordination bonds between metal ions/clusters and multidentate organic ligands exhibit fascinating structural topologies and potential applications as functional solid materials. The title coordination polymer, poly[diaquabis(μ4-biphenyl-3,4′,5-tricarboxylato-κ4O3:O3′:O4′:O5)tris[μ2-1,4-bis(1H-imidazol-1-yl)benzene-κ2N3:N3′]dicopper(II)dicopper(I)], [CuII2CuI2(C15H7O6)2(C12H10N4)3(H2O)2]n, was crystallized from a mixture of biphenyl-3,4′,5-tricarboxylic acid (H3bpt), 1,4-bis(1H-imidazol-1-yl)benzene (1,4-bib) and copper(II) chloride in a water–CH3CN mixture under solvothermal reaction conditions. The asymmetric unit consists of two crystallographically independent Cu atoms, one of which is CuII, while the other has been reduced to the CuIion. The CuIIcentre is pentacoordinated by three O atoms from three bpt3−ligands, one N atom from a 1,4-bib ligand and one O atom from a coordinated water molecule, and the coordination geometry can be described as distorted trigonal bipyramidal. The CuIatom exhibits a T-shaped geometry (CuN2O) coordinated by one O atom from a bpt3−ligand and two N atoms from two 1,4-bib ligands. The CuIIatoms are extended by bpt3−and 1,4-bib linkers to generate a two-dimensional network, while the CuIatoms are linked by 1,4-bib ligands, forming one-dimensional chains along the [20\overline{1}] direction. In addition, the completely deprotonated μ4-η1:η1:η1:η1bpt3−ligands bridge one CuIand three CuIIcations along thea(or [100]) direction to form a three-dimensional framework with a (103)2(10)2(42.6.102.12)2(42.6.82.10)2(8) topologyviaa 2,2,3,4,4-connected net. An investigation of the magnetic properties indicated a very weak ferromagnetic behaviour.
Formulation of dynamical theory of X-ray diffraction for perfect crystals in the Laue case using the Riemann surface
Authors: Saka Takashi
Published: March 2016

The dynamical theory for perfect crystals in the Laue case was reformulated using the Riemann surface, as used in complex analysis. In the two-beam approximation, each branch of the dispersion surface is specified by one sheet of the Riemann surface. The characteristic features of the dispersion surface are analytically revealed using four parameters, which are the real and imaginary parts of two quantities specifying the degree of departure from the exact Bragg condition and the reflection strength. By representing these parameters on complex planes, these characteristics can be graphically depicted on the Riemann surface. In the conventional case, the absorption is small and the real part of the reflection strength is large, so the formulation is the same as the traditional analysis. However, when the real part of the reflection strength is small or zero, the two branches of the dispersion surface cross, and the dispersion relationship becomes similar to that of the Bragg case. This is because the geometrical relationships among the parameters are similar in both cases. The present analytical method is generally applicable, irrespective of the magnitudes of the parameters. Furthermore, the present method analytically revealed many characteristic features of the dispersion surface and will be quite instructive for further numerical calculations of rocking curves.
Symmetry-adapted digital modeling I. Axial symmetric proteins
Authors: Janner A.
Published: March 2016

Considered are axial symmetric proteins exemplified by the octameric mitochondrial creatine kinase, the Pyr RNA-binding attenuation protein, the D-aminopeptidase and the cyclophilin A–cyclosporin complex, with tetragonal (422), trigonal (32), pentagonal (52) and pentagonal (52) point-group symmetry, respectively. One starts from the protein enclosing form, which is characterized by vertices at points of a lattice (the form lattice) whose dimension depends on the point group. This allows the indexing of Cα's at extreme radial positions. The indexing is extended to additional residues on the basis of a finer lattice, the digital modeling lattice Λ, which includes the form lattice as a sublattice. This leads to a coarse-grained description of the protein. In the crystallographic point-group case, the planar indices are obtained from a projection of atomic positions along the rotation axis, taken as thezaxis. The planar indices of a Cαare then those of the nearest projected lattice point. In the non-crystallographic case, low indices are an additional requirement. The coarse-grained bead follows from the condition imposed on the residues selected to have azcoordinate within a band of value δ above and below the height of lattice points. The choice of δ permits a variation of the coarse-grained bead model. For example, the value δ = 0.5 leads to a fine-grained indexing of the full set of residues, whereas with δ = 0.25 one gets a coarse-grained model which includes only about half of these residues. Within this procedure, the indexing of the Cαonly depends on the choice of the digital modeling lattice and not on the value of δ. The characteristics which distinguish the present approach from other coarse-grained models of proteins on lattices are summarized at the end.
Symmetry-adapted digital modeling III. Coarse-grained icosahedral viruses
Authors: Janner A.
Published: March 2016

Considered is the coarse-grained modeling of icosahedral viruses in terms of a three-dimensional lattice (the digital modeling lattice) selected among the projected points in space of a six-dimensional icosahedral lattice. Backbone atomic positions (Cα's for the residues of the capsid and phosphorus atoms P for the genome nucleotides) are then indexed by their nearest lattice point. This leads to a fine-grained lattice point characterization of the full viral chains in the backbone approximation (denoted as digital modeling). Coarse-grained models then follow by a proper selection of the indexed backbone positions, where for each chain one can choose the desired coarseness. This approach is applied to three viruses, the Satellite tobacco mosaic virus, the bacteriophage MS2 and the Pariacoto virus, on the basis of structural data from the Brookhaven Protein Data Bank. In each case the various stages of the procedure are illustrated for a given coarse-grained model and the corresponding indexed positions are listed. Alternative coarse-grained models have been derived and compared. Comments on related results and approaches, found among the very large set of publications in this field, conclude this article.
New conformations of linear polyubiquitin chains from crystallographic and solution-scattering studies expand the conformational space of polyubiquitin
Authors: Thach Trung Thanh , Shin Donghyuk , Han Seungsu , Lee Sangho
Published: March 2016

The conformational flexibility of linkage-specific polyubiquitin chains enables ubiquitylated proteins and their receptors to be involved in a variety of cellular processes. Linear or Met1-linked polyubiquitin chains, associated with nondegradational cellular signalling pathways, have been known to adopt multiple conformations from compact to extended conformations. However, the extent of such conformational flexibility remains open. Here, the crystal structure of linear Ub2was determined in a more compact conformation than that of the previously known structure (PDB entry 3axc). The two structures differ significantly from each other, as shown by an r.m.s.d. between Cαatoms of 3.1 Å. The compactness of the linear Ub2structure in comparison with PDB entry 3axc is supported by smaller values of the radius of gyration (Rg; 18versus18.9 Å) and the maximum interatomic distance (Dmax; 55.5versus57.8 Å). Extra intramolecular hydrogen bonds formed among polar residues between the distal and proximal ubiquitin moieties seem to contribute to stabilization of the compact conformation of linear Ub2. An ensemble of three semi-extended and extended conformations of linear Ub2was also observed by small-angle X-ray scattering (SAXS) analysis in solution. In addition, the conformational heterogeneity in linear polyubiquitin chains is clearly manifested by SAXS analyses of linear Ub3and Ub4: at least three distinct solution conformations are observed in each chain, with the linear Ub3conformations being compact. The results expand the extent of conformational space of linear polyubiquitin chains and suggest that changes in the conformational ensemble may be pivotal in mediating multiple signalling pathways.
T-to-R switch of muscle fructose-1,6-bisphosphatase involves fundamental changes of secondary and quaternary structure
Authors: Barciszewski Jakub , Wisniewski Janusz , Kolodziejczyk Robert , Jaskolski Mariusz , Rakus Dariusz , Dzugaj Andrzej
Published: March 2016

Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and is a key enzyme of gluconeogenesis and glyconeogenesis and, more generally, of the control of energy metabolism and glucose homeostasis. Vertebrates, and notablyHomo sapiens, express two FBPase isoforms. The liver isozyme is expressed mainly in gluconeogenic organs, where it functions as a regulator of glucose synthesis. The muscle isoform is expressed in all cells, and recent studies have demonstrated that its role goes far beyond the enzymatic function, as it can interact with various nuclear and mitochondrial proteins. Even in its enzymatic function, the muscle enzyme is different from the liver isoform, as it is 100-fold more susceptible to allosteric inhibition by AMP and this effect can be abrogated by complex formation with aldolase. All FBPases are homotetramers composed of two intimate dimers: the upper dimer and the lower dimer. They oscillate between two conformational states: the inactive T form when in complex with AMP, and the active R form. Parenthetically, it is noted that bacterial FBPases behave somewhat differently, and in the absence of allosteric activators exist in a tetramer–dimer equilibrium even at relatively high concentrations. [Hineset al.(2007),J. Biol. Chem.282, 11696–11704]. The T-to-R transition is correlated with the conformation of the key loop L2, which in the T form becomes `disengaged' and unable to participate in the catalytic mechanism. The T states of both isoforms are very similar, with a small twist of the upper dimer relative to the lower dimer. It is shown that at variance with the well studied R form of the liver enzyme, which is flat, the R form of the muscle enzyme is diametrically different, with a perpendicular orientation of the upper and lower dimers. The crystal structure of the muscle-isozyme R form shows that in this arrangement of the tetramer completely new protein surfaces are exposed that are most likely targets for the interactions with various cellular and enzymatic partners. The cruciform R structure is stabilized by a novel `leucine lock', which prevents the key residue, Asp187, from locking loop L2 in the disengaged conformation. In addition, the crystal structures of muscle FBPase in the T conformation with and without AMP strongly suggest that the T-to-R transition is a discrete jump rather than a shift of an equilibrium smooth transition through multiple intermediate states. Finally, using snapshots from three crystal structures of human muscle FBPase, it is conclusively demonstrated that the AMP-binding event is correlated with a β→α transition at the N-terminus of the protein and with the formation of a new helical structure.
Diffraction-geometry refinement in theDIALSframework
Authors: Waterman David G. , Winter Graeme , Gildea Richard J. , Parkhurst James M. , Brewster Aaron S. , Sauter Nicholas K. , Evans Gwyndaf
Published: March 2016

Rapid data collection and modern computing resources provide the opportunity to revisit the task of optimizing the model of diffraction geometry prior to integration. A comprehensive description is given of new software that builds upon established methods by performing a single global refinement procedure, utilizing a smoothly varying model of the crystal lattice where appropriate. This global refinement technique extends to multiple data sets, providing useful constraints to handle the problem of correlated parameters, particularly for small wedges of data. Examples of advanced uses of the software are given and the design is explained in detail, with particular emphasis on the flexibility and extensibility it entails.
2-({5-[(4-Chlorophenoxy)methyl]-4-phenyl-4H-1,2,4-triazol-3-yl}sulfanyl)-N-phenylacetamide
Authors: Mague Joel T. , Mohamed Shaaban K. , Akkurt Mehmet , Bakhite Etify A. , Albayati Mustafa R.
Published: March 2016

The title molecule, C23H19ClN4O2S, is in an `extended' conformation. In the crystal, pairwise N—H...N and C—H...O hydrogen bonds lead to the formation of `stair-step' chains. C—H...π interactions further contribute to the consolidation of the molecular packing. The 4-chlorophenyl group is disordered over two sets of sites in a 0.948 (2):0.052 (2) ratio. The dihedral angle between the two components of the disordered chloro-substituted benzene ring is 15.76 (9) °.
2-[(E)-(2S,5R)-2-Isopropyl-5-methylcyclohexylidene]-N-methylhydrazine-1-carbothioamide
Authors: Oliveira Adriano Bof de , Beck Johannes , Daniels Jörg , Farias Renan Lira de
Published: March 2016

There are two molecules in the asymmetric unit of the title compound, C12H23N3S, which are linked by two strong N—H...S hydrogen bonds, building a non-centrosymmetric dimer with graph-set motifR22(8). The molecules are further connected by N—H...S interactions into a two-dimensional hydrogen-bonded polymeric structure along the [001] direction. The absolute structure is based on the refinement of the Flack parameter.
N-(4-Benzoylphenyl)pyridine-2-carbothioamide
Authors: Hanif Muhammad , Hartinger Christian G. , Shaheen Muhammad Ashraf , Tahir Muhammad Nawaz
Published: March 2016

In the asymmetric unit of the title compound, C19H14N2OS, two geometrically different molecules,AandB, are present. InA, the dihedral angles between the central benzene ring and pendant phenyl and pyridine groups are 56.79 (14) and 8.3 (2)°, respectively. The equivalent data for moleculeBare 54.08 (12) and 16.7 (2)°, respectively. An intramolecular N—H...N hydrogen bond closes anS(5) ring in each molecule and the S and O atoms have anantidisposition. In the crystal, molecules are linked by a single C—H...O interaction intoA+Bpairs.
Ethyl 3-({[(4-methylphenyl)carbamoyl]methyl}sulfanyl)-5,6-diphenylpyridazine-4-carboxylate
Authors: Mague Joel T. , Mohamed Shaaban K. , Akkurt Mehmet , Bakhite Etify A. , Albayati Mustafa R.
Published: March 2016

The packing in the crystal of the title molecule, C28H25N3O3S, is aided by intermolecular N—H...O and C—H...O hydrogen bonds. In the crystal, the ethyl group of the ester is disordered over two sets of sites with refined occupancies of 0.760 (8) and 0.240 (8).
1-Benzyl-5-nitro-1H-indazole
Authors: Boulhaoua Mohammed , Abdelahi Mohammed Mokhtar , Benchidmi Mohammed , Essassi El Mokhtar , Mague Joel T.
Published: March 2016

The asymmetric unit of the title compound, C14H11N3O2, contains two independent molecules linked by a C—H...O hydrogen bond. Pairs of neighboring dimeric units associateviaπ–π stacking interactions.
(4,4′-Dimethoxy-2,2′-bipyridine-κ2N,N′)bis[2-(pyridin-2-yl)phenyl-κC1]iridium(III) hexafluoridophosphate unknown solvate
Authors: Natsumi Yano , Yusuke Kataoka , Tatsuya Kawamoto , Makoto Handa
Published: March 2016

The asymmetric unit of the title complex, [Ir(C11H8N)2(C12H12N2O2)]PF6, comprises a [Ir(ppy)2(diMeO-bpy)]+cation (Hppy = 2-phenylpyridine and diMeO-bpy = 4,4′-dimethoxy-2,2′-bipyridine) and a PF6−anion. The IrIIIatom is coordinated by two anionic ppy−ligands, each coordinating in aC^Ncyclometalated mode, and one neutral diMeO-bpy ligand, leading to a distorted octahedral geometry defined by acis-C2N4donor set. Intermolecular C—F...H contacts lead to a three-dimensional architecture that define columns parallel toa. Unknown disordered solvent molecules reside in these columns with the electron density being treated with SQUEEZE [Spek (2015).Acta Cryst. C71, 9–18]. The unit-cell data do not reflect the presence of the unresolved solvent.
(4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane-κ8N2,O6)rubidium 4,4′-bipyridinidyl
Authors: Mayer Kerstin , Klein Wilhelm , Fässler Thomas F.
Published: March 2016

The crystal structure of the title salt, [Rb(C18H36N2O6)](C10H8N2), consists of Rb+cations sequestered by a [2.2.2]cryptand molecule and 4,4′-bipyridinidyl radical monoanions. Both entities are centred by special positions: the Rb+cation is located on a twofold rotation axis and the 4,4′-bipyridinidyl anion is located about an inversion centre, so half of each moiety form the asymmetric unit. The planar 4,4′-bipyridinidyl molecules and the complexed cations are arranged in the sense of a distorted rock salt type of structure.
The impact of case formulation meetings for teams
Authors: Whitton Clare , Small Michelle , Lyon Hayley , Barker Lyndsie , Akiboh Martina
Published: March 2016

Purpose

– The purpose of this paper is to investigate the impact of psychological case formulation meetings for staff in a secure forensic learning disability and autism service.

Design/methodology/approach

– In total, 89 of the attendees completed a questionnaire prior to the formulation meeting and then another questionnaire following attendance at a formulation meeting.

Findings

– The results indicate that staff found these to be a helpful, informative and a positive experience professionally and personally. The results suggest that the formulation meetings developed staffs’ psychological understanding about the patient and their problems, helped to increase their empathy towards the patient, increased consistency in the teams’ views, and that the staff felt listened to.

Research limitations/implications

– Psychological formulation meetings are established in the current service, and therefore this may be a contributing to factor to the lack of significant change found in some of the items. Therefore, it would be beneficial for future services to complete a service evaluation at a much earlier point of implementation, as this may impact the level of significance.

Originality/value

– The findings of this service evaluation suggest that formulation is a beneficial and useful tool for teams and would be a helpful tool for psychologists to use in the clinical work with teams.
Effectiveness of individual psychodynamic psychotherapy in disability psychotherapy
Authors: McInnis Erica Elaine
Published: March 2016

Purpose

– The purpose of this paper is to report effectiveness of disability psychotherapy with a male adult with a mild intellectual disability presenting with complex emotional and behavioural problems.

Design/methodology/approach

– An individual case study was used with repeated analytic, quantitative and qualitative measures. This reported progress from individual weekly disability psychotherapy of psychodynamic orientation within an emotional disability framework.

Findings

– Disability psychotherapy led to a reduction in emotional and behavioural problems, reduction in emotional disability and facilitated protective psychological growth. In total, 88 sessions resulted in cessation of problem behaviours when other approaches did not. Given this therapy is likely to be reserved for the most complex and severe of cases, this study suggests more sessions of psychotherapy are needed than inferred from previous studies of effectiveness (Beailet al., 2007). This is to promote a sense of self which facilitates psychological well-being.

Research limitations/implications

– Limitations of a single case study include generalisability, controlling other factors in real life settings and subjectivity from inclusion of analytical measures. Further studies and follow-up would determine longevity of benefits. Nevertheless disability psychotherapy can be effective and should be available in a culturally appropriate service to meet the diverse needs of people with intellectual disabilities.

Originality/value

– This case study adds to the limited body of evidence on effectiveness of psychotherapy for people with intellectual disabilities. It is novel to report formal outcomes from an emotional disability model (Frankish, 2013a) and the use of analytic and attachment outcome measures.