bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid Agrobacterium-mediated transformation of tobacco cotyledons using toothpicks
Authors: Yau Yuan-Yeu , Easterling Mona , Brennan Lindsey
Published: October 2017

Tobacco is a model plant for genetic transformation, with leaf-disk transformation being the most commonly used method for its transformation. One disadvantage of leaf-disk transformation is obtaining an adequately sized leaf. Cotyledons from young seedlings are considered too small and fragile to use. In an attempt to overcome this drawback, a protocol was developed using toothpicks as a tool to inoculate cotyledons ~2mm in diameter. Agrobacterium tumefaciens LBA4404 hosting two different plasmids (pC35.BNK.2 or pRB140-Bxb1-op) was used for transformation. Fifty-six putative transgenic shoots (T0) were obtained from pC35.BNK.2 transformation. Among them, 38 (68%) grew roots in kanamycin-containing medium. Approximately, 35% of transgenic lines contained a single-copy transgenic locus based on Mendelian inheritance analysis and chi-square (χ2) test of T1 seedlings from 17 lines. To simplify the protocol, water-prepared Agrobacterium inoculum was used in pRB140-Bxb1-op (containing gus gene) transformation. This resulted in ~35% putative T0 transgenic lines stained strong blue with GUS histochemical staining assay. Both sets of results demonstrate toothpick inoculation to be an effective approach for Agrobacterium-mediated tobacco cotyledon transformation. This reduces wait time required in existing leaf-disk transformation method using mature leaves. Removal of step requiring submersion of explants in Agrobacterium liquid culture, the protocol also has advantages by minimizing Agrobacterium overgrowth and maintaining explant fitness for later tissue-culturing.
Neurobehavioural Correlates of Obesity are Largely Heritable
Authors: Vainik Uku , Baker Travis , Dadar Mahsa , Zeighami Yashar , Michaud Andréanne , Zhang Yu , García Alanis José C. , Misic Bratislav , Collins D. Louis , Dagher Alain
Published: October 2017

Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioural factors such as brain morphology, cognitive performance, and personality. Here, we tested whether these neurobehavioural factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project (N=895 siblings). Phenotypically, cortical thickness findings supported the “right brain hypothesis” for obesity. Namely, increased BMI associated with decreased cortical thickness in right frontal lobe and increased thickness in the left frontal lobe, notably in lateral prefrontal cortex. In addition, lower thickness and volume in entorhinal-parahippocampal structures, and increased thickness in parietal-occipital structures in participants with higher BMI supported the role of visuospatial function in obesity. Brain morphometry results were supported by cognitive tests, which outlined a negative association between BMI and visuospatial function, verbal episodic memory, impulsivity, and cognitive flexibility. Personality-BMI correlations were inconsistent. We then aggregated the effects for each neurobehavioural factor for a behavioural genetics analysis and estimated each factor’s genetic overlap with BMI. Cognitive test scores and brain morphometry had 0.25 - 0.45 genetic correlations with BMI, and the phenotypic correlations with BMI were 77-89% explained by genetic factors. Neurobehavioural factors also had some genetic overlap with each other. In summary, obesity as measured by BMI has considerable genetic overlap with brain and cognitive measures. This supports the theory that obesity is inherited via brain function, and may inform intervention strategies.

Significance Statement

Obesity is a widespread heritable health condition. Evidence from psychology, cognitive neuroscience, and genetics has proposed links between obesity and the brain. The current study tested whether the heritable variance in body mass index (BMI) is explained by brain and behavioural factors in a large brain imaging cohort that included multiple related individuals. We found that the heritable variance in BMI had genetic correlations 0.25 - 0.45 with cognitive tests, cortical thickness, and regional brain volume. In particular, BMI was associated with frontal lobe asymmetry and differences in temporal-parietal perceptual systems. Further, we found genetic overlap between certain brain and behavioural factors. In summary, the genetic vulnerability to BMI is expressed in the brain. This may inform intervention strategies.
Movement of moths through riparian reserves within oil palm plantations
Authors: Gray Ross E. J. , Slade Eleanor M. , Chung Arthur Y. C. , Lewis Owen T.
Published: October 2017

Tropical forests are becoming increasingly fragmented through conversion to agriculture, with negative consequences for biodiversity. Movement of individuals among the remaining fragments is critical to allow populations of forest-dependent taxa to persist. In SE Asia, conversion of forests to oil palm plantations is a particular threat. Many oil palm dominated landscapes retain forested riparian reserves along streams and rivers, but the extent to which these riparian reserves are used for movement, relative to the oil palm matrix, is poorly understood. We used mark-release-recapture methods to investigate the movement of five moth taxa in riparian reserves connected to a continuous forest area within oil palm matrix in Sabah, Malaysian Borneo. Moths were recaptured on average 68m from the release point, and the mean time to recapture was between 2 and 3 days. Moths showed a significant tendency to move within forested riparian reserves than into adjacent oil palm. When moving within riparian reserves moths also showed a tendency to orient their movement away from the continuous forest into the riparian reserve rather than towards continuous forest or into oil palm. Overall, our results show a role for riparian reserves as movement corridors through oil palm plantations for some invertebrate species, strengthening the case for their retention and re-establishment.
Accurate, Sensitive, and Precise Multiplexed Proteomics using the Complement Reporter Ion Cluster
Authors: Sonnett Matthew , Yeung Eyan , Wühr Martin
Published: October 2017

Quantitative analysis of proteomes across multiple time points, organelles, and perturbations is essential for understanding both fundamental biology and disease states. The development of isobaric tags (e.g. TMT) have enabled the simultaneous measurement of peptide abundances across several different conditions. These multiplexed approaches are promising in principle because of advantages in throughput and measurement quality. However, in practice existing multiplexing approaches suffer from key limitations. In its simple implementation (TMT-MS2), measurements are distorted by chemical noise leading to poor measurement accuracy. The current state-of- the-art (TMT-MS3) addresses this, but requires specialized quadrupole-iontrap-Orbitrap instrumentation. The complement reporter ion approach (TMTc) produces high accuracy measurements and is compatible with many more instruments, like quadrupole-Orbitraps. However, the required deconvolution of the TMTc cluster leads to poor measurement precision. Here, we introduce TMTc+, which adds the modeling of the MS2- isolation step into the deconvolution algorithm. The resulting measurements are comparable in precision to TMT-MS3/MS2. The improved duty cycle, and lower filtering requirements make TMTc+ more sensitive than TMT-MS3 and comparable with TMT-MS2. At the same time, unlike TMT-MS2, TMTc+ is exquisitely able to distinguish signal from chemical noise even outperforming TMT-MS3. Lastly, we compare TMTc+ to quantitative label-free proteomics of total HeLa lysate and find that TMTc+ quantifies 7.8k versus 3.9k proteins in a 5-plex sample. At the same time the median coefficient of variation improves from 13% to 4%. Thus, TMTc+ advances quantitative proteomics by enabling accurate, sensitive, and precise multiplexed experiments on more commonly used instruments.
Reconstruction of atomistic structures from coarse-grained models for protein-DNA complexes
Authors: Shimizu Masahiro , Takada Shoji
Published: October 2017

While coarse-grained (CG) simulations have widely been used to accelerate structure sampling of large biomolecular complexes, they are unavoidably less accurate and thus the reconstruction of all-atom (AA) structures and the subsequent refinement is of desire. In this study we developed an efficient method to reconstruct AA structures from sampled CG protein-DNA complex models, which attempts to model protein-DNA interface accurately. First we developed a method to reconstruct atomic details of DNA structures from a 3-site per nucleotide CG model, which uses a DNA fragment library. Next, for the protein-DNA interface, we referred to the sidechain orientations in the known structure of the target interface when available. The other parts are modeled by existing tools. We confirmed the accuracy of the protocol in various aspects including the structure deviation in the self-reproduction, the base pair reproducibility, atomic contacts at the protein-DNA interface, and feasibility of the posterior AA simulations.
Mid-Infrared Spectroscopy Study of Effects of Neonicotinoids on Forager Honey Bee (Apis mellifera) Fat Bodies and Their Connection to Colony Collapse Disorder
Authors: Feng Yuzheng , Luthra Aryan , Ding Kaiwen , Yang Yang , Savage Jordan , Wei Xinrui , Moeschter Roland , Ahuja Sachin , Villegas Victor , Torbina Bogdana , Ahooja Anjuli , Ellis Tom , Ellis Tom , Boechler Anna-Maria , Roberts Andrew
Published: October 2017

This study investigated the negative effects of neonicotinoid pesticides on honey bees in environment surrounding areas of pesticide use. The aim of the experiment is to identify possible contributors to the sudden decrease in honey bee population over the past 60 years, a phenomenon known as Colony Collapse Disorder. Analysis was performed on three sets of bees: the control group which was not in contact with pesticides, the infected dead group which was a set of bees suspected to have died due to neonicotinoids, and the infected alive group which was suspected to be under the influence of neonicotinoids. After dissecting the bee samples and extracting their fat bodies, the chemical composition and protein structures of the samples were analyzed using Mid-Infrared Beamline at the Canadian Light Source. Results from the spectra of bee samples exposed to neonicotinoids demonstrated possible residual pesticide chemicals within fat bodies. Several spectral peaks were also correlated with a possible change in protein secondary structures from primarily β-sheet to α-helix within fat bodies of neonicotinoid-affected bees. It is likely that the pesticides caused the growth of additional α-helical structures, which is consistent with consequences of the inhibition of nicotinic acetylcholine receptors (nAChRs) a current pathway of harm of Colony Collapse Disorder as identified in past literature.
Title: Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors
Authors: Yanagawa Masataka , Hiroshima Michio , Togashi Yuichi , Abe Mitsuhiro , Yamashita Takahiro , Shichida Yoshinori , Murata Masayuki , Ueda Masahiro , Sako Yasushi
Published: October 2017

G protein-coupled receptors (GPCRs) are major drug targets and have high potential for drug discovery. The development of a method for measuring the activities of GPCRs is essential for pharmacology and drug screening. However, it is difficult to measure the effects of a drug by monitoring the receptor on the cell surface, and changes in the concentrations of downstream signaling molecules, which depend on signaling pathway selectivity of the receptor, are used as an index of the receptor activity. Here, we show that single-molecule imaging analysis provides an alternative method for assessing ligand effects on GPCR. We monitored the dynamics of the diffusion of metabotropic glutamate receptor 3 (mGluR3), a class C GPCR, under various ligand conditions by using total internal reflection fluorescence microscopy (TIRFM). The single-molecule tracking analysis demonstrates that changes in the average diffusion coefficient of mGluR3 quantitatively reflect the ligand-dependent activity. Then, we reveal that the diffusion of receptor molecules is altered by the common physiological events associated with GPCRs, including G protein binding or accumulation in clathrin-coated pits, by inhibition experiments and dual-color single-molecule imaging analysis. We also confirm the generality of agonist-induced diffusion change in class A and B GPCRs, demonstrating that the diffusion coefficient is a good index for estimating the ligand effects on many GPCRs regardless of the phylogenetic groups, chemical properties of the ligands, and G protein-coupling selectivity.

One Sentence Summary:Single-molecule imaging for evaluating ligand effects on GPCRs by monitoring the diffusion dynamics on the cell surface.
The small molecule KHS101 induces bioenergetic dysfunction in glioblastoma cells through inhibition of mitochondrial HSPD1
Authors: Polson Euan S. , Kuchler Verena B. , Abbosh Christopher , Ross Edith M. , Mathew Ryan K. , Beard Hester A. , Chuntharpursat-Bon Eulashini , Williams Jennifer , Silva Bárbara Da , Shao Hao , Patel Anjana , Davies Adam J. , Droop Alastair , Griffiths Hollie B.S. , Chumas Paul , Short Susan C. , Lorger Mihaela , Gestwicki Jason , Roberts Lee D. , Bon Robin S. , Allison Simon J. , Zhu Shoutian , Markowetz Florian , Wurdak Heiko
Published: October 2017

Pharmacological inhibition of uncontrolled cell growth with small molecule inhibitors is a potential strategy against glioblastoma multiforme (GBM), the most malignant primary brain cancer. Phenotypic profiling of the neurogenic small molecule KHS101 revealed the chemical induction of lethal cellular degradation in molecularly-diverse GBM cells, independent of their tumor subtype, whereas non-cancerous brain cells remained viable. Mechanism-of-action (MOA) studies showed that KHS101 specifically bound and inhibited the mitochondrial chaperone HSPD1. In GBM but not non-cancerous brain cells, KHS101 elicited the aggregation of an enzymatic network that regulates energy metabolism. Compromised glycolysis and oxidative phosphorylation (OXPHOS) resulted in the metabolic energy depletion in KHS101-treated GBM cells. Consistently, KHS101 induced key mitochondrial unfolded protein response factor DDIT3in vitroandin vivo, and significantly reduced intracranial GBM xenograft tumor growth upon systemic administration, without discernible side effects. These findings suggest targeting of HSPD1-dependent oncometabolic pathways as an anti-GBM therapy.
Gender- and gamete-specific patterns of X chromosome segregation in a three-gendered nematode
Authors: Tandonnet Sophie , Farrell Maureen C. , Koutsovoulos Georgios , Blaxter Mark , Parihar Manish , Sadler Penny L. , Shakes Diane , Pires da Silva Andre
Published: October 2017

Meiosis is at the core of sexual reproduction and alterations to its program can have dramatic effects. In this study, we investigate the segregation pattern of the X chromosome in Auanema rhodensis, a three-gendered nematode. This species has an atypical pattern of X chromosome segregation during male spermatogenesis that results in the exclusive production of haplo-X sperm. Here we use a combination of genetic and cytological approaches to show that while XX females undergo conventional meiosis to produce mostly haplo-X oocytes, hermaphrodites undergo atypical meiosis to produce nullo-X oocytes and mostly diplo-X sperm. Gender- and gamete-specific alterations of the normal meiotic program include non-pairing of the X homologs and precocious separation of X chromatids. Given these intra-species, intra-individual and intra-gametogenesis variations in meiotic program of A. rhodensis, we argue that it is an ideal model to study the plasticity of meiosis and how it can be modulated.
Population-based analysis of ocularChlamydia trachomatisin trachoma-endemic West African communities identifies genomic markers of disease severity
Authors: Last AR , Pickering H , Roberts Ch , Coll F , Phelan J , Burr SE , Cassama E , Nabicassa M , Seth-Smith HMB , Hadfield J , Cutcliffe LT , Clarke IN , Mabey DCW , Bailey RL , Clark TG , Thomson NR , Holland MJ
Published: October 2017

Chlamydia trachomatis(Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. UsingCtwhole genome sequences obtained directly from conjunctival swabs, we studiedCtgenomic diversity and associations betweenCtgenetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea Bissau, West Africa. All sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion intrpAresulting in a truncated non-functional protein and the ocular tyrosine repeat regions present intarPassociated with ocular tissue localization. We have identified twenty-oneCtnon-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs withinpmpD(OR=4.07,p*=0.001) andtarP(OR=0.34,p*=0.009). Eight SNPs associated with disease severity were found inyjfH (rlmB)(OR=0.13,p*=0.037),CTA0273(OR=0.12,p*=0.027),trmD(OR=0.12,p*=0.032),CTA0744(OR=0.12,p*=0.041),glgA(OR=0.10,p*=0.026),alaS(OR=0.10,p*=0.032),pmpE(OR=0.08,p*=0.001) and the intergenic regionCTA0744-CTA0745(OR=0.13,p*=0.043). This study demonstrates the extent of genomic diversity within a naturally circulating population of ocularCt, and the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocularCtpathogenesis and disease transmission.
A fast immune priming that confers a complete infection resistance on silkworm (Bombyx mori)
Authors: Miyashita Atsushi
Published: October 2017

I have previously reported an immune priming in silkworm triggered by peptidoglycans, which is long-lasting but slow-acting. Here I report a faster immune priming, which can be triggered by an injection of gelatin or collagen, that confers a complete infection resistance to Gram-negative bacteria on silkworms. Gelatin-injected silkworms showed 100% viability in a lethal dose of a Gram-negative bacterial infection within two hours after the gelatin injection. Injection of collagen showed a similar effect. Whereas, an injection of non-gelatin protein (bovine serum albumin) solution did not induce such reaction. These results suggest that the silkworm possesses a fast and gelatin-inducible pathway that confers infection resistance to Gram-negative bacteria, which may act as a front-line defense. This finding highlights the potency of gelatin as a tool for investigating the primed immune responses in insect species.
Changes in corticospinal excitability associated with motor learning by observing
Authors: McGregor Heather R. , Vesia Michael , Rinchon Cricia , Chen Robert , Gribble Paul L.
Published: October 2017

While many of our motor skills are acquired through physical practice, we can also learn how to make movements by observing others. For example, individuals can learn how to reach in novel dynamical environments (‘force fields’, FF) by observing the movements of a tutor. Previous neurophysiology and neuroimaging studies in humans suggest a role for the motor system in motor learning by observing. Here we tested the role of primary motor cortex (M1) in motor learning by observing. We used single-pulse transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in right hand muscles at rest. MEPs were elicited before and after participants observed either a video adapting her reaches to a FF or a control video showing a tutor performing reaches in an unlearnable FF. We predicted that observing motor learning would increase M1 excitability to a greater extent than observing movements that did not involve learning. We found that observing FF learning increased MEP amplitudes recorded from right first dorsal interosseous (FDI) and right abductor pollicis brevis (APB) muscles. There were no changes in MEP amplitudes for control participants who observed a tutor performing reaches in an unlearnable, randomly varying FF. The observed MEP changes can thus be specifically linked to observing motor learning. These results are consistent with the idea that observing motor learning produces functional changes in M1, or corticospinal networks or both.
Analytic combinatorics for bioinformatics I: seeding methods
Authors: Filion Guillaume J.
Published: October 2017

Seeding heuristics are the most widely used strategies to speed up sequence alignment in bioinformatics. Such strategies are most successful if they are calibrated, so that the speed-versus-accuracy trade-off can be properly tuned. In the widely used case of read mapping, it has been so far impossible to predict the success rate of competing seeding strategies for lack of a theoretical framework. Here I present an approach to estimate such quantities based on the theory of analytic combinatorics. In a nutshell, the strategy is to specify a combinatorial construction of reads where the seeding heuristic fails, translate this specification into a generating function using formal rules, and finally extract the probabilities of interest from the singularities of the generating function. I use this approach to construct simple estimators of the success rate of the seeding heuristic under different types of sequencing errors. I also show how the analytic combinatorics strategy can be used to compute the associated type I and type II error rates (mapping the read to the wrong location, or being unable to map the read). Finally, I show how analytic combinatorics can be used to estimate average quantities such as the expected number of errors in reads where the seeding heuristic fails. Overall, this work introduces a theoretical and practical framework to find the success rate of seeding heuristics and related problems in bioinformatics.
Default Mode Network in Temporal Lobe epilepsy: interactions with memory performance
Authors: Zanão Tamires Araujo , Martins Lopes Tátila , Machado de Campos Brunno , Nogueira Mateus Henrique , Yasuda Clarissa Lin , Cendes Fernando
Published: October 2017

Objective

to investigate abnormal functional connectivity in the resting-state default mode network (DMN) and its relation to memory impairments in patients with temporal lobe epilepsy with and without hippocampal sclerosis (HS)

Method

we enrolled 122 MTLE patients divided into right-HS (n=42), left-HS (n=49), MRI-negative MTLE (n=31) and controls (n=69). All underwent resting-state seed-based connectivity fMRI, with a seed placed at the posterior cingulate cortex, an essential node for the DMN. In addition, patients and 41 controls were tested for verbal and visual memory, estimated intelligence coefficient and delayed recall.

Results

Both right-HS and MRI-negative group presented the poorest visual memory scores, and right-HS and left-HS had a worse performance in verbal memory compared to controls and MRI-negative groups. As expected, hippocampus was less connected than controls in all groups of patients. Although EEGs indicated that 64.5% of MRI-negative patients were lateralized to the left, this group showed activations similar to the right-HS.

Conclusion

Our data suggest that there is a disruption of the normal pattern of DMN in MTLE. Patients with left and right-HS presented similar, increased and decreased connectivity in the ipsilateral hemisphere; however, left-HS had abnormal decreased connectivity in the contralateral hemisphere. Per neuropsychological examination, the presence of HS in the left hemisphere had more impact on verbal memory, which was not found when the seizure focus is in the left hemisphere in the absence of HS. The absence of hippocampal atrophy seems to yield a less prominent disruption in both functional connectivity and neuropsychological performance.
Minimization of muscle activation costs demanded from mechanical work and power accounts for selection of duty factor in human gaits
Authors: Sobota Grzegorz , Usherwood James R.
Published: October 2017

Duty factor DF – the proportion of a stride a foot is in contact with the ground – is of fundamental mechanical importance, and is often viewed as a defining kinematic parameter distinguishing walking (DF>0.5) from running (DF<0.5). However, the mechanical and/or physiological considerations that determine duty factor are not well understood. Here, a model is proposed that focuses on the interaction between mechanical and muscle costs to account for duty factor in human gaits. It minimizes the activation costs associated with mechanical work or power demand during muscle contraction (whichever is the more demanding). Empirical observations match model predictions using initial muscle parameters over a range of speeds within gaits. However, a better match is achieved – and a better account for the walk-run transition – with tuned muscle parameters. The tuned model is validated with responses in duty factor to walking at a range of imposed, unnatural step frequencies.
DNA-stabilized silver nanoclusters as specific, ratiometric fluorescent dopamine sensors
Authors: Del Bonis-O’Donnell Jackson T. , Thakrar Ami , Wain Hirschberg Jeremy , Vong Daniel , Queenan Bridget N. , Fygenson Deborah K. , Pennathur Sumita
Published: October 2017

Neurotransmitters are small molecules that orchestrate complex patterns of brain activity. Unfortunately, there exist few sensors capable of directly detecting individual neurotransmitters. Those sensors that do exist are either unspecific or fail to capture the temporal or spatial dynamics of neurotransmitter release. DNA-stabilized silver nanoclusters (DNA-AgNCs) are a new class of biocompatible, fluorescent nanostructures that have recently been demonstrated to offer promise as biosensors. In this work, we identify two different DNA sequences which form dopamine-sensitive nanoclusters. We demonstrate that each sequence supports two distinct DNA-AgNCs capable of providing specific, ratiometric fluorescent sensing of dopamine concentration in vitro. DNA-Ag nanoclusters therefore offer a novel, low-cost approach to quantification of dopamine, creating the potential for real-time monitoring in vivo.
Ets2 anchors the prometastatic function of mutant p53 in osteosarcoma
Authors: Liu Daniel D. , Kang Yibin
Published: October 2017

Mutations in the tumor suppressor p53 occur in a majority of human cancers. Some gain-of-function (GOF) p53 mutations endow tumor cells with increased metastatic ability, although our understanding of the underlying mechanism remains incomplete. In this issue of Genes & Development, Pourebrahim and colleagues (pp. 1847–1857) develop a new mouse model of osteosarcoma in which a GOF mutant p53 allele is expressed specifically in osteoblasts, while the tumor microenvironment remains wild type for p53, allowing for the study of cell-autonomous functions. In this model, the role of GOF mutant p53 in promoting lung metastasis is shown to be critically dependent on the transcription factor Ets2 and is accompanied by the elevated expression of a cluster of small nucleolar RNAs (snoRNAs).
Asymmetric structure of cis-[N-(9-anthracenylmethyl)-1,2-ethanediamine]dipyridineplatinum(II) dinitrate
Authors: Kiwada Tatsuto , Takayama Hiroshi , Hirasaki Aika , Ogawa Kazuma , Odani Akira
Published: October 2017

Platinum antitumour agents, containing aromatic rings, which are used for targeting DNA in effective therapies for the treatment of cancer. We have synthesized the title metallocomplex with an aromatic ligand and determined its crystal structure. In many cases, complexes of platinum and other metals have a symmetrical structure. In contrast, the platinum(II) complex with pyridine and N-(9-anthracenylmethyl)-1,2-ethanediamine as ligands (systematic name: cis-{N-[(anthracen-9-yl)methyl]ethane-1,2-diamine-κ2
N,N′}bis(pyridine-κN)platinum(II) dinitrate), [Pt(C5H5N)2(C17H18N2)](NO3)2, is asymmetric. Of the two pyridine ligands, only one is π-stacked with anthracene, resulting in an asymmetric structure. Moreover, the angle of orientation of each pyridine ligand is variable. Further examination of the packing motif confirms an intermolecular edge-to-face interaction.
Synergy among phase-refinement techniques in macromolecular crystallography
Authors: Burla Maria Cristina , Cascarano Giovanni Luca , Giacovazzo Carmelo , Polidori Giampiero
Published: October 2017

Ab initioand non-ab initiophasing methods are often unable to provide phases of sufficient quality to allow the molecular interpretation of the resulting electron-density maps. Phase extension and refinement is therefore a necessary step: its success or failure can make the difference between solution and nonsolution of the crystal structure. Today phase refinement is trusted to electron-density modification (EDM) techniques, and in practice to dual-space methods which try,viasuitable constraints in direct and in reciprocal space, to generate higher quality electron-density maps. The most popular EDM approaches, denoted here as mainstream methods, are usually part of packages which assist crystallographers in all of the structure-solution steps from initial phasing to the point where the molecular model perfectly fits the known features of protein chemistry. Other phase-refinement approaches that are based on different sources of information, denoted here as out-of-mainstream methods, are not frequently employed. This paper aims to show that mainstream and out-of-mainstream methods may be combined and may lead to dramatic advances in the present state of the art. The statement is confirmed by experimental tests using molecular-replacement, SAD–MAD andab initiotechniques.
Exploring differences between private and public organizations in business excellence models
Authors: Raharjo Hendry , Eriksson Henrik
Published: October 2017

Purpose

The purpose of this paper is to explore the differences between public and private organizations in the paths of business excellence models and to identify the key drivers for creating business results and customer satisfaction.

Design/methodology/approach

The partial least squares structural equation modeling technique is used to compare the path coefficients and to identify the key driver constructs for creating business results.

Findings

The variation in endogenous constructs is found to be more difficult to explain or predict for private organizations than for public organizations, despite the fact that the performance of private organizations is almost always higher than or equal to the performance of public ones in all criteria. The effect of “leadership” on “management of processes” is significantly higher in public organizations than in private ones. However, “management of processes” in public organizations does not seem to translate into “results.” The effect of “strategic planning” on creating business “results” is negative for public organizations and remains inconclusive, due to insufficient evidence, for private organizations.

Research limitations/implications

The results may not be generally applicable to other countries. However, they do support the move toward more tailor-made models for specific sectors.

Practical implications

It is necessary to review the national business excellence model in order to fit specific sectors.

Originality/value

This is the first study to investigate the differences between private and public organizations in the Swedish business excellence model.
A quality system’s impact on the service experience
Authors: Smith Jeffery , Anderson Sidney , Fox Gavin
Published: October 2017

Purpose

The purpose of this paper is to examine the interplay between technical and social systems within an organization that potentially affect the service experience, as perceived by end customers.

Design/methodology/approach

The paper explores the potential impact of an integrated service quality system on the service experience. A conceptual model is presented, accompanied by a detailed development of the hypotheses. Two samples (Study 1:n=474, Study 2:n=225) of consumers are used to empirically test the proposed model.

Findings

The analysis reveals the impact a technical system has on employees’ inherent abilities (i.e. the social system), which, in turn, affect the overall assessment by customers. Additionally, the situation in which an employee works (i.e. operating environmental conditions) results in differences in the model.

Research limitations/implications

This paper’s main implication is this paper employs established theory to develop a model that is empirically tested to show that implementing and maintaining a quality-oriented service system can positively influence the overall customer experience. The limitations are based primarily on the methodology in which individual employees assessed all aspects of both the social and technical systems.

Practical implications

Managers should be diligent in their design and implementation of the quality components as these affect the work setting in which employees operate.

Originality/value

Prior research has neither explored an integrated service quality system’s impact on the service experience nor employed an established theoretical framework. This work accomplishes both with the results providing contributions to both theory and practice.
State of government accounting in Ghana and Benin: a “tentative” account
Authors: Lassou Philippe Jacques Codjo
Published: October 2017

Purpose

The purpose of this paper is to examine the state of government accounting in Ghana and Benin using neo-patrimonial and organizational façade lenses.

Design/methodology/approach

The study used two country case studies that engaged with stakeholders including donors, civil society, politicians, and civil servants. Semi-structured interviews were used as the main data collection technique, which were complemented by document analysis.

Findings

The study finds that government accounting reforms are decoupled and used in both countries as a façade which is caused, to a varying degree, by indigenous neo-patrimonial governance traits of informal institutions, patronage, and clientelism. And despite the relatively superior Ghanaian system, in terms of its functioning, compared to the Beninese, government accounting plays a more symbolic role in the former than in the latter.

Originality/value

This is one of the very few theoretically informed empirical studies that examine the state of government accounting in the two major African settings – Anglophone and Francophone. The results inform policies more tailored to indigenous governance issues for better outcomes.
Deferring felony prosecution: a process evaluation of an innovative Cook County State’s Attorney’s Office program
Authors: Cossyleon Jennifer , Orwat John , George Christine , Stemen Don , Key Whitney
Published: October 2017

Purpose

The Cook County State Attorneys’ Deferred Prosecution Program (DPP) is a pre-trial diversionary program that accepts first-time, non-violent defendants charged with a felony crime. The purpose of this paper is to document the development, implementation, and program patterns of the DPP to better understand the program’s scope and reach in diverting defendants from traditional criminal prosecution.

Design/methodology/approach

The approach to evaluating Cook County’s DPP is primarily qualitative. Through interviews with program administrators and current and former participants, the authors document the process of creating and implementing such DPP that aims to avoid a felony conviction altogether. The authors provide program participant patterns to shed light on the program’s scope and reach in diverting defendants from traditional felony prosecution.

Findings

Using data from staff, administrators, and program participants, the authors found that the DPP was developed and implemented through supportive leadership who instilled a culture of collaboration and buy-in. Expanding the program could include increasing the capacity of DPP to include additional participants or having a DPP incorporated into each branch court, instead of the centralized system under which it currently operates. Increasing the capacity and scope of the program could both further decrease criminal court caseloads and most importantly avoid a higher number of stigmatizing felony convictions for first-time non-violent defendants.

Practical implications

DPPs are cost effective and can be easily implemented within existing systems. Collaboration and buy-in from all stakeholders are crucial to the program’s success. DPP offers opportunities for expansion. Increasing the capacity and scope of the program could both further decrease criminal court caseloads and most importantly avoid a higher number of stigmatizing felony convictions for first-time non-violent felony defendants.

Originality/value

The main goals of DPP were two-fold. The first was to minimize the level of resources allocated for non-violent offenders in the criminal justice system by diverting such defendants out of the criminal justice system early in the process and reducing the recidivism rates of program participants. The second aimed to provide an option for eligible defendants to avoid a felony conviction, thereby avoiding the collateral consequences associating with a felony conviction.
US public views toward biosocial risk factors for criminality: a brief report
Authors: Berryessa Colleen M.
Published: October 2017

Purpose

The purpose of this paper is to present preliminary survey data measuring attitudes of members of the US public on the importance, existence, and potential legal use of biological risk factors for criminality.

Design/methodology/approach

Survey data were collected from an online sample of US public in conjunction with an experiment not included in this report.

Findings

Data suggest that the public generally agrees that there are certain biological characteristics that make one more likely to exhibit criminality. The public does not appear to agree on whether or not this type of evidence should be allowed in court, but the large majority of respondents were worried about its potential misuse.

Practical implications

Social risk factors were generally viewed by respondents as more important to explaining criminality, suggesting that sociological views of crime may be still more prevalent in the lay public. Worries about biosocial risk factor evidence being misused in court have been previously discussed in academic literature, but the public also appears to share these concerns. The public especially worries that this kind of evidence could be used to incorrectly excuse an offender’s behavior, showing that they may be weary of this evidence in court as potential jurors. Attitudes of many members of the public on these issues may be affected by academic disagreement in the criminology community on the importance of these issues.

Originality/value

Scholars have emphasized the need for discussion on how the US public views biosocial risk factors for criminality. As there are no known data of this type, these data are the first of their kind.
Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation‐induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2
Authors: Jiang Wen‐Bin , Zhao Wei , Chen Hao , Wu You‐Yang , Wang Yi , Fu Guo‐Sheng , Yang Xiang‐Jun
Published: October 2017

Baicalin, a flavonoid glycoside separated from Scutellaria baicalensis, has cardioprotection against ischaemia/reperfusion (I/R) injury. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is considered as an endogenous protective mechanism against I/R injury depending on its anti‐oxidant and anti‐apoptotic characteristics. The present study demonstrates whether ALDH2 contributes to the cardioprotection of baicalin against hypoxia/reoxygenation (H/R)‐inudced H9c2 cardiomyocytes injury. Our results observed that H/R treatment resulted in a significant decrease in cells viability and obvious increases in caspase‐3 activity and apoptosis rate in H9c2 cells, while these alterations were evidently reversed by baicalin pretreatment. Simultaneously, baicalin mitigated H/R‐induced the decreases in the levels of ALDH2 mRNA and protein as well as the activity of ALDH2 in H9c2 cells. However, we found that daidzin, an ALDH2 antagonist, remarkably attenuated baicalin‐elicited inhibitory action on H/R‐induced the downregulation of cells viability and Bcl‐2 protein expression, and the upregulations of caspase‐3 activity, apoptosis rate, cytochrome c and Bax proteins expressions in H9c2 cells. In addition, baicalin reversed H/R‐induced oxidative stress as evidenced by the downregulation of malondialdehyde (MAD) and 4‐hydroxy aldehydes (4‐HNE) levels, the inhibition of endogenous reactive oxygen species (ROS) generation, and the downregulation of superoxide dismutase (SOD) activity induced by H/R treatment, while these effects were also blocked by daidzin. Furthermore, we found that Alda‐1, an ALDH2 agonist, also abolished H/R‐induced cytotoxicity, apoptosis, and oxidative stress, indicating that ALDH2 mediated H/R‐induced H9c2 cell injury. Overall, these results suggested that baicalin prevents H/R‐induced apoptosis and oxidative stress through enhancing ALDH activity and expression in H9c2 cardiomyocytes.
Rising Drug Costs Drives the Growth of Pharmacy Benefit Managers Exclusion Lists: Are Exclusion Decisions Value‐Based?
Authors: Cohen Joshua P. , Khoury Christelle El , Milne Christopher‐Paul , Peters Sandra M.
Published: October 2017

Objective

We examine whether drugs’ excluded versus recommended status on pharmacy benefit manager exclusion lists corresponds to evidence from cost‐effectiveness analyses, lack of evidence, or rebates.

Data Sources

To find cost‐effectiveness data for drugs on 2016 exclusion lists of CVS Caremark and Express Scripts, we searched the Tufts Cost‐Effectiveness Analysis Registry and the peer‐reviewed literature.

Study Design

For each excluded and recommended drug, we compared the mean cost‐per‐QALY, and we calculated the difference between the numbers of excluded and recommended drugs for which we could find no cost‐effectiveness evidence.

Data Collection

As keywords in our searches, we used the brand and generic drug name and “cost‐effectiveness” and “cost‐per‐quality‐adjusted life‐year.” Of 240 retrieved studies, 110 were selected for analysis.

Principal Findings

The mean cost‐per‐QALY for excluded drugs was higher ($51,611) than the cost‐per‐QALY for recommended drugs ($49,474), but not statistically significant. We could find no cost‐effectiveness evidence in the Registry or peer‐reviewed literature for 23 of the excluded drugs, and no evidence for 5 of the recommended drugs.

Conclusions

Cost‐effectiveness does not correlate with a drug's excluded or recommended status. Lack of cost‐effectiveness evidence favors a drug's excluded status.
Exploring the Roles of Vernacular Accounting Systems in the Development of “Enabling” Global Accounting and Control Systems
Authors: Goretzki Lukas , Strauss Erik , Wiegmann Leona
Published: October 2017

This study sheds light on how self‐developed local accounting and control systems (so‐called vernacular accounting systems;VAS) can influence knowledge integration in development processes of enabling global accounting and control systems. We focus on accounting and control systems as devices that enable local actors to build on codified knowledge to create “new” knowledge that can facilitate local problem solving. We argue that local actors would evaluate a proposed global system as enabling or coercive depending on both their ability to manipulate the knowledge codified within as well as the consequences that the codified knowledge has for their authority in the local knowledge creation process. Based on a case study of the development process of a global accounting and control system, we demonstrate thatVAScan play a crucial role in both local actors’ evaluation of a proposed system (as points of reference) and their influence on knowledge integration (as knowledge transformation devices). Furthermore, local actors may continue to rely on theirVASif they realize that the proposed global system does not fit their needs. Local actors can thus use theirVAS(as negotiation devices) to strengthen their position in the development process as counterparts to the global system designers because the “threat” of continuing to use theVASmay prompt system designers to integrate local knowledge into the proposed global system. We thus also suggest that, if made visible to others and actively mobilized,VASmay foster productive debates that facilitate the migration of local knowledge into global systems.
Onset of labour epidural analgesia with low‐dose bupivacaine and different doses of fentanyl
Authors: Vedagiri Sai R. , Singh S. I. , Qasem F. , Nguyen D. , Dhir S. , Marmai K. , Adam R. , Jones P. M.
Published: October 2017

This study investigated the effects of different doses of epidural fentanyl on the time to onset of epidural analgesia in women in early labour. We hypothesised that onset of epidural labour analgesia (the primary outcome defined as time in minutes from completion of epidural bolus to the first uterine contraction with a numeric pain rating scale [NPRS] score ≤ 3) would be faster with 100 μg of fentanyl epidural bolus compared with 20 μg or 50 μg. Epidural labour analgesia was initiated with 20 μg of fentanyl (F20 group), 50 μg (F50 group) or 100 μg (F100 group) along with 10 ml bupivacaine 0.08% as the loading dose. We randomly allocated 105 patients, with 35 patients in each group. Median (IQR [range]) time to achieve NPRS ≤ 3 was 18 (11–30 [6–20]) min in F20, 10 (8–19 [4–30]) min in F50 and 10 (6–16 [3–30]) min in F100 groups. There was a significant difference in onset times comparing F100 with F20 (p < 0.001) and F50 with F20 (p = 0.007), but not significantly different comparing F100 with F50 (p = 0.19). The median (IQR [range]) time from the epidural loading dose to first patient controlled epidural analgesia bolus was 61 min (20–165 [20–420]) in F20, 118 min (66–176 [20–396]) in F50 and 150 min (66–214 [30‐764]) in F100 groups. This was not statistically significant (p = 0.16) comparing the F20 with the F100 group. There were no significant differences in maternal side‐effects, mode of delivery, patient satisfaction scores or neonatal Apgar scores between all groups. We conclude that the 50 μg and 100 μg fentanyl doses were associated with reduced onset times to effective analgesia compared with the 20 μg dose.
Catecholaminergic polymorphic ventricular tachycardia, an update
Authors: Pérez‐Riera Andrés R. , Barbosa‐Barros Raimundo , de Rezende Barbosa Marianne P. C. , Daminello‐Raimundo Rodrigo , de Lucca Augusto A. , de Abreu Luiz C.
Published: October 2017

Catecholaminergic polymorphic ventricular tachycardia is a rare devastating lethal inherited disorder or sporadic cardiac ion channelopathy characterized by unexplained syncopal episodes, and/or sudden cardiac death (SCD), aborted SCD (ASCD), or sudden cardiac arrest (SCA) observed in children, adolescents, and young adults without structural heart disease, consequence of adrenergically mediated arrhythmias: exercise‐induced, by acute emotional stress, atrial pacing, or β‐stimulant infusion, even when the electrocardiogram is normal. The entity is difficult to diagnose in the emergency department, given the range of presentations; thus, a familiarity with and high index of suspicion for this pathology are crucial. Furthermore, recognition of the characteristic findings and knowledge of the management of symptomatic patients are necessary, given the risk of arrhythmia recurrence and SCA. In this review, we will discuss the concept, epidemiology, genetic background, genetic subtypes, clinical presentation, electrocardiographic features, diagnosis criteria, differential diagnosis, and management.