bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle metabolism
Authors: Tardif Nicolas , Grip Jonathan , Rooyackers Olav
Published: May 2017

Purpose of review

To review the recent findings on metabolic derangements leading to loss of muscle mass and function.

Recent findings

Several recent studies investigated methods to assess muscle mass and function and its clinical relevance. These are also included. A few studies confirm that a low muscle mass is related to a worse outcome but also a compromised muscle function at discharge is related to long-term survival. A low quality of muscle assessed by the density of muscle from a computed tomography scan is related to mortality. For the metabolic derangements, a compromised handling of calcium is present in muscle of animal models and might be causing a decreased muscle function in patients. Transcriptomics analyses of muscle post-ICU indicated an upregulation of regenerative pathways, but still muscle mass is not recovering in most patients. This could be due to an impairment regenerative capacity due to satellite cells dysfunction.

Muscle mass and function are related to outcome. New finding show that not only muscle mass but also muscle quality is important, that a compromised handling of calcium might be involved in muscle weakness and that regaining muscle could be compromised due to a defective regenerative capacity of satellite cells.
CHD4 as a Potential Biomarker in Differentiating Between Cellular Schwannoma and Malignant Peripheral Nerve Sheath Tumor
Authors: Wu Chun-Chieh , Pan Mei-Ren , Wei Yu-Ching , Lin Chih-Hung , Yang Sheau-Fang , Tsai Hung-Pei , Luo Chi-Wen , Chai Chee-Yin
Published: May 2017

Cellular schwannoma is an uncommon variant of benign peripheral nerve sheath tumors, but is commonly misdiagnosed as malignant peripheral sheath tumor (MPNST). Conventional methods that are used to distinguish cellular schwannoma from MPNST include immunohistochemistry (IHC) staining. However, most markers cannot precisely differentiate these 2 tumor types, and thus identification of a better marker is needed to improve the accuracy of diagnosis. Here, we evaluate the use of chromodomain helicase DNA-binding protein 4 (CHD4) as a specific marker for cellular schwannoma by comparing CHD4 and S-100 IHC staining in 14 cellular schwannoma and 17 MPNST tissue samples. Our results indicated that nuclear CHD4 stains were in moderate-to-high in 94% MPNST (16 cases) and 93% cellular schwannoma (13 cases). However, cytoplasmic CHD4 stains were moderate-to-high in 93% cellular schwannoma (13 cases) but negative-to-weak in 100% MPNST (17 cases). In contrast, the S-100 stains were moderate-to-high in 86% of the cellular schwannoma (12 cases) and in 35% of the MPNST (6 cases). Taken together, the results indicated that different location of CHD4 staining is a potential biomarker to differentiate cellular schwannoma from MPNST.
The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die*
Authors: Weiss Scott L. , Balamuth Fran , Hensley Josey , Fitzgerald Julie C. , Bush Jenny , Nadkarni Vinay M. , Thomas Neal J. , Hall Mark , Muszynski Jennifer
Published: May 2017

Objective:

The epidemiology of in-hospital death after pediatric sepsis has not been well characterized. We investigated the timing, cause, mode, and attribution of death in children with severe sepsis, hypothesizing that refractory shock leading to early death is rare in the current era.

Design:

Retrospective observational study.

Setting:

Emergency departments and ICUs at two academic children’s hospitals.

Patients:

Seventy-nine patients less than 18 years old treated for severe sepsis/septic shock in 2012–2013 who died prior to hospital discharge.

Interventions:

None.

Measurements and Main Results:

Time to death from sepsis recognition, cause and mode of death, and attribution of death to sepsis were determined from medical records. Organ dysfunction was assessed via daily Pediatric Logistic Organ Dysfunction-2 scores for 7 days preceding death with an increase greater than or equal to 5 defined as worsening organ dysfunction. The median time to death was 8 days (interquartile range, 1–12 d) with 25%, 35%, and 49% of cumulative deaths within 1, 3, and 7 days of sepsis recognition, respectively. The most common cause of death was refractory shock (34%), then multiple organ dysfunction syndrome after shock recovery (27%), neurologic injury (19%), single-organ respiratory failure (9%), and nonseptic comorbidity (6%). Early deaths (≤ 3 d) were mostly due to refractory shock in young, previously healthy patients while multiple organ dysfunction syndrome predominated after 3 days. Mode of death was withdrawal in 72%, unsuccessful cardiopulmonary resuscitation in 22%, and irreversible loss of neurologic function in 6%. Ninety percent of deaths were attributable to acute or chronic manifestations of sepsis. Only 23% had a rise in Pediatric Logistic Organ Dysfunction-2 that indicated worsening organ dysfunction.

Conclusions:

Refractory shock remains a common cause of death in pediatric sepsis, especially for early deaths. Later deaths were mostly attributable to multiple organ dysfunction syndrome, neurologic, and respiratory failure after life-sustaining therapies were limited. A pattern of persistent, rather than worsening, organ dysfunction preceded most deaths.
Technical Feasibility of a Combined Noncontrast Magnetic Resonance Protocol for Preoperative Transcatheter Aortic Valve Replacement Evaluation
Authors: Cannaò Paola M. , Muscogiuri Giuseppe , Schoepf U. Joseph , De Cecco Carlo N. , Suranyi Pal , Lesslie Virginia W. , Piccini Davide , Giri Shivraman , Varga-Szemes Akos
Published: May 2017

Purpose:

The aim of this study was to prospectively evaluate the technical feasibility of a noncontrast magnetic resonance angiography (MRA) protocol using investigational prototype self-navigated 3D (SN3D) radial whole-heart and quiescent-interval single-shot (QISS) pulse sequences regarding their potential in planning transcatheter aortic valve replacement (TAVR).

Materials and Methods:

Five patients (76±7 y) with severe aortic valve stenosis and prior computed tomographic angiography (CTA) for TAVR planning and 10 healthy volunteers (28±6 y) underwent noncontrast MRA on a 1.5 T system. A SN3D whole-heart acquisition was used to assess the aortic root anatomy. Evaluation of the aortoiliac access route was performed with both SN3D and QISS. Measurements were compared among SN3D, QISS, and CTA using a paired t test or 1-way analysis of variance. Image quality ratings and contrast-to-noise ratios (CNR) were analyzed using Mann-Whitney U tests. Interobserver agreement was evaluated using Cohen’s κ.

Results:

The combined SN3D and QISS protocol provided a 10.1±1.6-minute acquisition time. TAVR-relevant evaluation was technically feasible in healthy volunteers. All measurements showed good agreement with CTA in patients (all P>0.098). SN3D and QISS produced similar image quality both in volunteers and in patients (all P>0.122). There was no difference in qualitative ratings between MRA and CTA (all P>0.119). Interobserver agreement was good for MRA (κ=0.71 to 0.76) and excellent for CTA (κ=0.82 to 0.84). Thoracic SN3D provided a similar CNR compared with CTA (P=0.117). CTA yielded higher CNR in the abdominopelvic region compared with QISS (P=0.006).

Conclusions:

A noncontrast MRA protocol combining SN3D and QISS acquisitions for the assessment of cardiac and vascular access route anatomy has technical feasibility for TAVR planning.
Lung Density and Pulmonary Artery Diameter are Predictors of Pulmonary Hypertension in Systemic Sclerosis
Authors: Bakker Margreet E. , Ninaber Maarten K. , Stolk Jan , Kroft Lucia J.M. , Schouffoer Anne A. , de Vries Bouwstra Jeska K. , van Wijngaarden Suzanne E. , Stoel Berend C.
Published: May 2017

Purpose:

The aim was to evaluate computed tomography (CT)-measured pulmonary artery diameter (PAD) and lung density as predictors of pulmonary hypertension (PH) in subjects with systemic sclerosis (SSc). We compared these PAD values with normal values and between SSc subgroups with PH and/or interstitial lung disease (ILD). We investigated whether PAD predicts PH and whether lung densitometry, by using the 85th percentile density value (Perc85) as a measure for ILD, can predict PH.

Materials and Methods:

PAD and Perc85 were measured in axial CT scans and compared between 54 SSc and 76 control subjects. Four SSc subgroups were defined on the basis of PH (systolic PA pressure ≥35 mm Hg) and/or ILD (fibrosis score ≥7): PH−/ILD−, PH−/ILD+, PH+/ILD−, and PH+/ILD+. The association of PAD with age, body mass index, Perc85, lung function, and hemodynamic measures was investigated using univariate correlation along with the predictive value of these measures with respect to PH.

Results:

PAD in SSc was larger than that in controls (30.1±4.9 vs. 26.9±2.7 mm,P<0.001). PH+ patients showed increased PAD compared with PH− patients (34.2±4.2 vs. 28.6±4.3 mm,P<0.001), where PH+/ILD+ subjects showed the widest diameter (34.6±4.1 mm). In SSc patients, hemodynamic measures, age, body mass index, Perc85, and lung function correlated with PAD. PAD was best explained by Perc85, together with age (R2=0.358). PAD best predicted PH (AUC, 0.877;P<0.001), and PAD≥30.7 mm showed 80% sensitivity and 87% specificity. Perc85 also predicted PH (AUC, 0.733;P=0.024).

Conclusions:

In subjects with SSc, lung density and PAD are CT markers, each with predictive value for PH.
Surgeon Experience and Medicare Expenditures for Laparoscopic Compared to Open Colectomy
Authors: Sheetz Kyle H. , Ibrahim Andrew M. , Regenbogen Scott E. , Dimick Justin B.
Published: May 2017

Objective:

To quantify the extent to which payments for laparoscopic and open colectomy are influenced by a surgeon's experience with laparoscopy.

Background:

Numerous studies suggest that healthcare costs for laparoscopic colectomy are lower than open surgery. None have assessed the importance of surgeon experience on the relative financial benefits of laparoscopy.

Methods:

We conducted a study of 182,852 national Medicare beneficiaries undergoing laparoscopic or open colectomy between 2010 and 2012. Using instrumental variable methods to account for selection bias, we compared Medicare payments for laparoscopic and open colectomy. We stratified our analysis by surgeons’ annual experience with laparoscopic colectomy to determine the influence of provider experience on payments.

Results:

In the fully adjusted analysis, average episode payments per patient were $2640 [95% confidence interval (CI) −$4091 to −$1189] lower with the laparoscopic approach versus open. Surgeons in the highest quartile of laparoscopic experience demonstrated an average payment savings of $5456 per patient (CI −$7918 to −$2994) in their laparoscopic versus open cases. Among surgeons in the lowest quartile of laparoscopic experience, there was, however, no difference between laparoscopic and open cases (difference: $954, 95% CI −$731 to $2639). Differences in payments were explained by differences in complications rates. Both groups had similar rates of complications for open procedures (least experience, 21%, most experience, 21%; P = 0.45), but differed significantly on rates of complications for laparoscopic cases (least experience, 28%, most experience, 15%; P < 0.01).

Conclusions:

This population-based study demonstrates that differences in payments between laparoscopic and open colectomy are influenced by surgeon experience. The laparoscopic approach does not reduce payments for patients whose surgeons have limited experience with the procedure.
Distinct pattern of epigenetic DNA modification in leukocytes from patients with colorectal carcinoma and individuals with precancerous conditions, benign adenoma and inflammatory bowel disease – a link to oxidative stress
Authors: Starczak Marta , Zarakowska Ewelina , Modrzejewska Martyna , Dziaman Tomasz , Szpila Anna , Linowiecka Kinga , Guz Jolanta , Szpotan Justyna , Gawronski Maciej , Labejszo Anna , Liebert Ariel , Banaszkiewicz Zbigniew , Klopocka Maria , Foksinski Marek , Gackowski Daniel , Olinski Ryszard
Published: May 2017

A characteristic feature of malignant cells, including colorectal cancer cells, is a profound decrease in level of 5-hydroxymethylcytosine, product of 5-methylcytosine oxidation by TET enzymes. This study included four groups of subjects: healthy controls, and patients with inflammatory bowel disease (IBD), benign polyps and colorectal cancer. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2’-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of vitamin C and A. Expressions of TET1 and TET2 turned out to be the highest in IBD group. To the best of our knowledge, this is the first study to show that healthy subjects, individuals with precancerous conditions and colorectal cancerpatients present with distinct specific patterns of epigenetic modifications in leukocyte DNA.
Static and dynamic DNA loops form AP-1 bound activation hubs during macrophage development
Authors: Phanstiel Douglas H. , Van Bortle Kevin , Spacek Damek , Hess Gaelen T. , Shamim Muhammad Saad , Machol Ido , Love Michael I. , Aiden Erez Lieberman , Bassik Michael C. , Snyder Michael P.
Published: May 2017

The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops during human monocyte-to-macrophage differentiation. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer-activation of preformed loops represent two distinct modes of regulation that together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for Activator Protein 1 (AP-1) binding events, suggesting multi-loop activation hubs driven by cell-type specific transcription factors may represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.

HIGHLIGHTS

High resolution and high sensitivity of loop detection via deeply sequenced in situ Hi-C experiments during monocyte to macrophage differentiation (> 10 billion total reads)

Multi-loop interaction communities identified surrounding key macrophage genes.

Multi-loop communities connect dynamic enhancers through both static and newly acquired DNA loops, forming hubs of activation

Macrophage activation hubs are enriched for AP-1 bound long-range enhancer interactions, suggesting cell-type specific TFs drive changes in 3D structure and transcription through regulatory DNA loops
Characterizing the structure-function relationship of a naturally-occurring RNA thermometer
Authors: Meyer Sarai , Lucks Julius B.
Published: May 2017

A wide number of bacteria have been found to govern virulence and heat shock responses using temperature-sensing RNAs known as RNA thermometers. A prime example is theagsAthermometer known to regulate the production of the AgsA heat shock protein inSalmonella entericausing a “fourU” structural motif. Using the SHAPE-Seq RNA structure-probing methodin vivoandin vitro, we found that the regulator functions by a subtle shift in equilibrium RNA structure populations that lead to a partial melting of the helix containing the ribosome binding site. We also demonstrate that ribosome binding to theagsAmRNA causes changes to the thermometer structure that appear to facilitate thermometer helix unwinding. These results demonstrate how subtle RNA structural changes can govern gene expression and illuminate the function of an important bacterial regulatory motif.
Pheno4J: a gene to phenotype graph database
Authors: Mughal Sajid , Moghul Ismail , Yu Jing , Clark Tristan , Gregory David S , Pontikos Nikolas
Published: May 2017

Efficient storage and querying of large amounts of genetic and phenotypic data is crucial to contemporary clinical genetic research. This introduces computational challenges for classical relational databases, due to the sparsity and sheer volume of the data. Our Java based solution loads annotated genetic variants and well phenotyped patients into a graph database to allow fast efficient storage and querying of large volumes of structured genetic and phenotypic data. This abstracts technical problems away and lets researchers focus on the science rather than the implementation. We have also developed an accompanying webserver with end-points to facilitate querying of the database.

Availability and Implementation

The Java code and python code is available athttps://github.com/phenopolis/pheno4i

Contact

n.pontikos@ucl.ac.uk
Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition
Authors: Mahadevan Vivek , Khademullah C. Sahara , Dargaei Zahra , Chevrier Jonah , Uvarov Pavel , Kwan Julian , Bagshaw Richard D. , Pawson Tony , Emili Andrew , DeKoninck Yves , Anggono Victor , Airaksinen Matti S. , Woodin Melanie A.
Published: May 2017

KCC2 is a neuron-specific K+-Cl−cotransporter essential for establishing the Cl−gradient required for hyperpolarizing inhibition. KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to numerous human neurological disorders including epilepsy and neuropathic pain. Using unbiased functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function. Our analysis revealed that KCC2 interacts with a diverse set of proteins, and its most predominant interactors play important roles in postsynaptic receptor recycling. The most abundant KCC2 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons significantly increases KCC2 expression and hyperpolarizes the reversal potential for Cl−. Overall, our global native-KCC2 interactome and subsequent characterization revealed PACSIN1 as a novel and potent negative regulator of KCC2.
Mosaic chromosomal aneuploidy detection by sequencing (MAD-seq)
Authors: Kong Yu , Berko Esther R. , Marcketta Anthony , Maqbool Shahina B. , Simões-Pires Claudia A. , Kronn David F. , Ye Kenny Q. , Suzuki Masako , Auton Adam , Greally John M.
Published: May 2017

Current approaches to detect and characterize mosaic chromosomal aneuploidy are limited by sensitivity, efficiency, cost or the need to culture cells. We describe a combination of a new sequencing-based assay and a novel analytical approach that allows low levels of mosaicism for chromosomal aneuploidy to be detected, assigned to a meiotic or mitotic origin, and quantified as a proportion of the cells in the sample. We show results from a multi-ethnic assay design that is suitable for populations of diverse racial and ethnic origins, and how theMADSEQanalytical approach applied to exome sequencing data reveals unrecognized aneuploidy in 1000 Genomes samples and cell lines from public repositories. We have made the assay design and analytical software open for unrestricted use, with the goal that it can be applied in clinical samples to allow new insights into the unrecognized prevalence of mosaic chromosomal aneuploidy and its phenotypic associations.
Evaluating fast maximum likelihood-based phylogenetic programs using empirical phylogenomic data sets
Authors: Zhou Xiaofan , Shen Xingxing , Hittinger Chris Todd , Rokas Antonis
Published: May 2017

Phylogenetics has witnessed dramatic increases in the sizes of data matrices assembled to resolve branches of the tree of life, motivating the development of programs for fast, yet accurate, inference. For example, several different fast programs have been developed in the very popular maximum likelihood framework, including RAxML/ExaML, PhyML, IQ-TREE, and FastTree. Although these four programs are widely used, a systematic evaluation and comparison of their performance using empirical genome-scale data matrices has so far been lacking. To address this question, we evaluated these four programs on 19 empirical phylogenomic data sets from diverse animal, plant, and fungal lineages with respect to likelihood maximization, tree topology, and computational speed. For single-gene tree inference, we found that the more exhaustive and slower strategies (ten searches per alignment) outperformed faster strategies (one tree search per alignment) using RAxML, PhyML, or IQ-TREE. Interestingly, single-gene trees inferred by the three programs yielded comparable coalescent-based species tree estimations. For concatenation–based species tree inference, IQ-TREE consistently achieved the best-observed likelihoods for all data sets, and RAxML/ExaML was a close second. In contrast, PhyML often failed to complete concatenation-based analyses, whereas FastTree was the fastest but generated lower likelihood values and more dissimilar tree topologies in both types of analyses. Finally, data matrix properties, such as the number of taxa and the strength of phylogenetic signal, sometimes substantially influenced the relative performance of the programs. Our results provide real-world gene and species tree phylogenetic inference benchmarks to inform the design and execution of large-scale phylogenomic data analyses.
CA1 and CA3 differentially support spontaneous retrieval of episodic contexts within human hippocampal subfields
Authors: Dimsdale-Zucker Halle R. , Ritchey Maureen , Ekstrom Arne D. , Yonelinas Andrew P. , Ranganath Charan
Published: May 2017

The hippocampus plays a critical role in spatial and episodic memory. Mechanistic models predict that hippocampal subfields have computational specializations that differentially support memory. However, there is little empirical evidence suggesting differences between the subfields, particularly in humans. To clarify how hippocampal subfields support human spatial and episodic memory, we developed a virtual reality paradigm where participants passively navigated through houses (spatial contexts) across a series of videos (episodic contexts). We then used multivariate analyses of high-resolution fMRI data to identify neural representations of contextual information during recollection. Multi-voxel pattern similarity analyses revealed that CA1 represented objects that shared an episodic context as more similar than those from different episodic contexts. CA23DG showed the opposite pattern, differentiating between objects encountered in the same episodic context. The complementary characteristics of these subfields explain how we can parse our experiences into cohesive episodes while retaining the specific details that support vivid recollection.
Scalable preprocessing for sparse scRNA-seq data exploiting prior knowledge
Authors: Mukherjee Sumit , Zhang Yue , Fan Joshua , Seelig Georg , Kannan Sreeram
Published: May 2017

Motivation

Single cell RNA-seq (scRNA-seq) data contains a wealth of information which has to be inferred computationally from the observed sequencing reads. As the ability to sequence more cells improves rapidly, existing computational tools suffer from three problems. (1) The decreased reads-per-cell implies a highly sparse sample of the true cellular transcriptome. (2) Many tools simply cannot handle the size of the resulting datasets. (3) Prior biological knowledge such as bulk RNA-seq information of certain cell types or qualitative marker information is not taken into account. Here we present UNCURL, a preprocessing framework based on non-negative matrix factorization for scRNA-seq data, that is able to handle varying sampling distributions, scales to very large cell numbers and can incorporate prior knowledge.

Results

We find that preprocessing using UNCURL consistently improves performance of commonly used scRNA-seq tools for clustering, visualization, and lineage estimation, both in the absence and presence of prior knowledge. Finally we demonstrate that UNCURL is extremely scalable and parallelizable, and runs faster than other methods on a scRNA-seq dataset containing 1.3 million cells.

Availability

Source code is available athttps://github.com/yjzhang/uncurl_python

Contact

ksreeram@uw.edu,gseelig@uw.edu
The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
Authors: Herriges Michael J. , Tischfield David J. , Cui Zheng , Morley Michael P. , Han Yumiao , Babu Apoorva , Li Su , Lu MinMin , Cendan Isis , Garcia Benjamin A. , Anderson Stewart A. , Morrisey Edward E.
Published: May 2017

A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA–TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)–Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in cis to promote Nkx2.1 transcription. Although loss of NANCI alone does not adversely affect lung development, concurrent heterozygous mutations in both NANCI and Nkx2.1 leads to persistent Nkx2.1 deficiency and reprogramming of lung epithelial cells to a posterior endoderm fate. This disruption in the NANCI–Nkx2.1 gene duplex results in a defective perinatal innate immune response, tissue damage, and progressive degeneration of the adult lung. These data point to a mechanism in which lncRNAs act as rheostats within lncRNA–TF gene duplex loci that buffer TF expression, thereby maintaining tissue-specific cellular identity during development and postnatal homeostasis.
Wnt5a promotes Frizzled-4 signalosome assembly by stabilizing cysteine-rich domain dimerization
Authors: DeBruine Zachary J. , Ke Jiyuan , Harikumar Kaleeckal G. , Gu Xin , Borowsky Peter , Williams Bart O. , Xu Wenqing , Miller Laurence J. , Xu H. Eric , Melcher Karsten
Published: May 2017

Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal “thumb” and a disulfide-stabilized C-terminal “index finger,” yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers. Each dimer is stabilized by interactions of one hydrophobic palmitoleic acid tail with two CRD palmitoleoyl-binding grooves oriented end to end, suggesting that the Wnt palmitoleoyl group stimulates CRD–CRD interaction. Using bioluminescence resonance energy transfer (BRET) in live cells, we show that WNT5A stimulates dimerization of membrane-anchored FZD4 CRDs and oligomerization of full-length FZD4, which requires the integrity of CRD palmitoleoyl-binding residues. These results suggest that FZD receptors may form signalosomes in response to Wnt binding through the CRDs and that the Wnt palmitoleoyl group is important in promoting these interactions. These results complement our understanding of lipoprotein receptor-related proteins 5 and 6 (LRP5/6), Dishevelled, and Axin signalosome assembly and provide a more complete model for Wnt signalosome assembly both intracellularly and at the membrane.
Dinuclear cobalt(II) complexes with double phosphate ester bridges and tetradentate ligands having anisole or quinoline appendages
Authors: Anjana S. S. , Varghese Babu , Prasad Edamana
Published: May 2017

Phosphate esters provide a rigid and stable polymeric backbone in nucleic acids. Metal complexes with phosphate ester groups have been synthesized as structural and spectroscopic models of phosphate-containing enzymes. Dinucleating ligands are used extensively to synthesize model complexes since they provide the support required to stabilize such complexes. The crystal structures of two dinuclear CoII complexes, namely bis(μ-diphenyl phosphato-κ2
O:O′)bis({2-methoxy-N,N-bis[(pyridin-2-yl)methyl]aniline-κ4
N,N′,N′′,O}cobalt(II)) bis(perchlorate), [Co(C12H10O4P)2(C19H19N3O)2](ClO4)2, and bis(μ-diphenyl phosphato-κ2
O:O′)bis({N,N-bis[(pyridin-2-yl)methyl]quinolin-8-amine-κ4
N,N′,N′′,O}cobalt(II)) bis(perchlorate), [Co(C12H10O4P)2(C21H18N4)2](ClO4)2, with tetradentate 2-methoxy-N,N-bis[(pyridin-2-yl)methyl]aniline (L
1) and N,N-bis[(pyridin-2-yl)methyl]quinolin-8-amine (L
2) ligands are reported. The complexes have similar structures, with distorted octahedral geometries around the metal centres. Both are centrosymmetric (Z′ = 0.5), with the CoII centres doubly bridged by diphenyl phosphate ester groups. A number of aromatic–aromatic interactions are present and differ between the two complexes as the anisole group in L
1 is replaced by a quinoline group in L
2. A detailed study of these interactions is presented.
Crystal structure of 5-chloro-N
1-(5-phenyl-1H-pyrazol-3-yl)benzene-1,2-diamine
Authors: Yartsev Yegor , Palchikov Vitaliy , Gaponov Alexandr , Shishkina Svitlana
Published: May 2017

The title compound, C15H13ClN4, crystallizes with two independent molecules (A and B) in the asymmetric unit, which are far from planar as a result of steric repulsion between the rings. The benzene and phenyl rings are inclined to the central pyrazole ring by 46.64 (10) and 17.87 (10)° in molecule A, and by 40.02 (10) and 14.18 (10)° in molecule B. The aromatic rings are inclined to one another by 58.77 (9)° in molecule A, and 36.95 (8)° in molecule B. In the crystal, the A and B molecules are linked by two pairs of N—H...N hydrogen bonds forming A–B dimers. These are further linked by a fifth N—H...N hydrogen bond, forming tetramer-like units that stack along the a-axis direction, forming columns, which are in turn linked by C—H...π interactions, forming layers parallel to the ac plane.
Crystal structure of a silver-, cobalt- and iron-based phosphate with an alluaudite-like structure: Ag1.655Co1.64Fe1.36(PO4)3
Authors: Bouraima Adam , Makani Thomas , Assani Abderrazzak , Saadi Mohamed , El Ammari Lahcen
Published: May 2017

The new silver-, cobalt- and iron-based phosphate, silver cobalt iron tris(orthophosphate), Ag1.655Co1.64Fe1.36(PO4)3, was synthesized by solid-state reactions. Its structure is isotypic to that of Na2Co2Fe(PO4)3, and belongs to the alluaudite family, with a partial cationic disorder, the AgI atoms being located on an inversion centre and twofold rotation axis sites (Wyckoff positions 4a and 4e), with partial occupancies of 0.885 (2) and 0.7688 (19), respectively. One of the two P atoms in the asymmetric unit completely fills one 4e site while the Co and Fe atoms fill another 4e site, with partial occupancies of 0.86 (5) and 0.14 (5), respectively. The remaining Co2+ and Fe3+ cations are distributed on a general position, 8f, in a 0.39 (4):0.61 (4) ratio. All O atoms and the other P atoms are in general positions. The structure is built up from zigzag chains of edge-sharing [MO6] (M = Fe/Co) octahedra stacked parallel to [101]. These chains are linked together through PO4 tetrahedra, forming polyhedral sheets perpendicular to [010]. The resulting framework displays two types of channels running along [001], in which the AgI atoms (coordination number eight) are located.
Crystal structure of calcium dinickel(II) iron(III) tris(orthophosphate): CaNi2Fe(PO4)3
Authors: Ouaatta Said , Assani Abderrazzak , Saadi Mohamed , El Ammari Lahcen
Published: May 2017

The title compound, CaNi2Fe(PO4)3, was synthesized by solid-state reactions. Its structure is closely related to that of α-CrPO4 in the space group Imma. Except for two O atoms in general positions, all atoms are located in special positions. The three-dimensional framework is built up from two types of sheets extending parallel to (100). The first sheet is made up from two edge-sharing [NiO6] octahedra, leading to the formation of [Ni2O10] double octahedra that are connected to two PO4 tetrahedra through a common edge and corners. The second sheet results from rows of corner-sharing [FeO6] octahedra and PO4 tetrahedra forming an infinite linear chain. These layers are linked together through common corners of PO4 tetrahedra and [FeO6] octahedra, resulting in an open three-dimensional framework that delimits two types of channels parallel to [100] and [010] in which the eightfold-coordinated CaII cations are located.
Three closely related (2E,2′E)-3,3′-(1,4-phenylene)bis[1-(methoxyphenyl)prop-2-en-1-ones]: supramolecular assemblies in one dimension mediated by hydrogen bonding and C—H...π interactions
Authors: Sim Aijia , Chidan Kumar C. S. , Kwong Huey Chong , Then Li Yee , Win Yip-Foo , Quah Ching Kheng , Naveen S. , Chandraju S. , Lokanath N. K. , Warad Ismail
Published: May 2017

In the title compounds, (2E,2′E)-3,3′-(1,4-phenylene)bis[1-(2-methoxyphenyl)prop-2-en-1-one], C26H22O4 (I), (2E,2′E)-3,3′-(1,4-phenylene)bis[1-(3-methoxyphenyl)prop-2-en-1-one], C26H22O4 (II) and (2E,2′E)-3,3′-(1,4-phenylene)bis[1-(3,4-dimethoxyphenyl)prop-2-en-1-one], C28H26O6 (III), the asymmetric unit consists of a half-molecule, completed by crystallographic inversion symmetry. The dihedral angles between the central and terminal benzene rings are 56.98 (8), 7.74 (7) and 7.73 (7)° for (I), (II) and (III), respectively. In the crystal of (I), molecules are linked by pairs of C—H...π interactions into chains running parallel to [101]. The packing for (II) and (III), features inversion dimers linked by pairs of C—H...O hydrogen bonds, forming R
2
2(16) and R
2
2(14) ring motifs, respectively, as parts of [201] and [101] chains, respectively.
Synthesis and crystal structures of three new benzotriazolylpropanamides
Authors: Amenta Donna S. , Liebing Phil , Biero Julia E. , Sherman Robert J. , Gilje John W. , Edelmann Frank T.
Published: May 2017

The base-catalyzed Michael addition of 2-methylacrylamide to benzotriazole afforded 3-(1H-benzotriazol-1-yl)-2-methylpropanamide, C10H12N4O (1), in 32% yield in addition to small amounts of isomeric 3-(2H-benzotriazol-2-yl)-2-methylpropanamide, C10H12N4O (2). In a similar manner, 3-(1H-benzotriazol-1-yl)-N,N-dimethylpropanamide, C11H14N4O (3), was prepared from benzotriazole andN,N-dimethylacrylamide. All three products have been structurally characterized by single-crystal X-ray diffraction. The crystal structures of1and2comprise infinite arrays formed by N—H...O and N—H...N bridges, as well as π–π interactions, while the molecules of3are aggregated to simple π-dimers in the crystal.
Bis[N-benzyl-N-(2-phenylethyl)dithiocarbamato-κ2S,S′](1,10-phenanthroline-κ2N,N′)zinc(II)
Authors: Sonia A. S. , Baskaran R. , Lokanath N. K. , Selvanayagam S.
Published: May 2017

In the title compound, [Zn(C16H16NS2)2(C12H8N2)], the ZnIIatom exists within an N2S4donor set that defines a distorted octahedral geometry; weak intramolecular C—H...S hydrogen bonds are noted. In the crystal, molecules are linkedviaweak C—H...π interactions, formingC(11) chains propagating along [001].
An online ASD learning module for pediatric health care professionals
Authors: Burnham Riosa Priscilla , Greenblatt Andrea , Muskat Barbara
Published: May 2017

Purpose

Youth with autism spectrum disorder (ASD) often have co-occurring health care needs and are likely to come into contact with several health care professionals over their lives. At the hospital, youth with ASD may require specialized supports to optimize health care experiences and for medical services to be delivered safely. At present, there is a limited understanding of how to best support this patient population. The purpose of this paper is to develop, implement, and evaluate an online training module for hospital staff about ASD.

Design/methodology/approach

To evaluate participants’ perceived utility of the learning tool, a post-module survey was administered.

Findings

In all, 102 health care professionals and other hospital staff completed the training and evaluation measure. Majority of participants had prior ASD-focused education (66 percent) and had experience working with at least 20 youths with ASD (57 percent). Majority of participants (88 percent) perceived the information from the module to be helpful in their daily work and reported that they learned something new (63 percent). Participants were interested in receiving additional ASD online module training opportunities on topics including: hands-on behavior management strategies, in-hospital resources, guidance on treatment adherence, and ASD training geared specifically to protection services staff.

Originality/value

The results from this evaluation have important practice implications for hospital staff working with patients with ASD and their families. Evidence-based strategies were easily accessible for staff and the module can be feasibly built upon and expanded as well as disseminated beyond the current hospital setting.
Quality of health and health services in people with fragile X syndrome: perspective of their parents
Authors: Seidel Michael
Published: May 2017

Purpose

People with fragile X syndrome (FXS), a monogenetic disorder with frequent autism spectrum disorder symptoms, are confronted with many health-related needs, especially concerning behavioural and mental problems. The number of publications about health inequalities or the usage of health services in persons with FXS is scarce in general. There is no information about the situation in Germany. The paper aims to discuss this issue.

Design/methodology/approach

Assessment of health status, access to, and satisfaction with health care in people with fragile X by a questionnaire completed by their parents.

Findings

A total of 74 questionnaires were included in the assessment. While children and adolescents with FXS often (40 per cent) utilised specialised services for the coordination of health-related services, adults most often made use of family doctors. Most parents described the health status of their relatives as good to excellent (89 per cent). However, the satisfaction with health care-related demands by family doctors, medical specialists, and psychotherapists was rated in the average to above average range.

Research limitations/implications

This paper is of special value as it gives insight into the perspective of parents concerning access to health care of FXS in Germany.

Originality/value

This paper gives a first insight concerning access of people with FXS to the German health care system.
Sustainable international tourist hotels: the role of the executive chef
Authors: Wan Tung-Hsuan , Hsu Yun-Shu , Wong Jehn-Yih , Liu Shin-Hao
Published: May 2017

Purpose

Human capital is the most important determinant of the Hospitality industry’s success. Executive chefs should be skilled in both management and culinary arts, in addition to ensuring the success of the entire hospitality division. The study aims to understand the competencies of executive chefs in international tourist hotels in Taiwan.

Design/methodology/approach

Literature review and behavioral event interviews were conducted with ten executive chefs and executive sous chefs. The modified Delphi method verified the results using 15 experts.

Findings

A competency framework was created, with four quadrants – managerial, operational, behaviors and skills – to classify executive chefs’ competencies. Each competency was further divided into sub-competencies – culinary research, emotional control, negotiation skills, job guidance and proactive thinking ability – for 25 items. Quadrants I and II are hard competencies that can be improved through education and training, whereas the third and fourth are soft competencies that require more time for development in workers.

Practical implications

The two-step study developed a competency framework with a practical reference value. The study results could be utilized by human resources managers during their companies’ training, recruitment, selection and promotion.

Originality/value

Besides the Delphi method, a deep behavioral event interview that enabled determining critical competencies was also used to collect data. The results obtained could be used to structure schools’ curricula. Collaborations between the hospitality industry and schools could help develop better curricula and training plans to maximize the availability of educational resources.
Impacts of misbehaving air passengers on frontline employees: role stress and emotional labor
Authors: Hu Hsin-Hui“Sunny” , Hu Hsin-Yi , King Brian
Published: May 2017

Purpose

The study aimed to investigate the impact of customer misbehaviors on airline in-flight customer contact personnel. A theoretical framework was proposed to test the meditating role of role stress and emotional labor in the relationship between consumer misbehaviors and emotional exhaustion.

Design/methodology/approach

In all, 336 cabin crew members employed by international airline companies participated in the study. The hypothesized model was tested using structural equation modeling with AMOS 20.0.

Findings

The results provide evidence that customer misbehaviors relate positively to employee role stress, emotional labor and emotional exhaustion. Moreover, role stress and emotional labor play important roles in enhancing the impacts of customer misbehaviors and thereby influence employee emotional exhaustion.

Practical implications

The findings potentially impact on employers both within and beyond the airline industry by demonstrating how frontline employees can be provided with support to reduce stress or exhaustion, leading ultimately to increased satisfaction.

Originality/value

This study has provided deeper theoretical insights into customer misbehaviors and their effects on employee role stress, emotional labor and emotional exhaustion.
Teacher learning through collaboration
Authors: Wood Keith
Published: May 2017

Purpose

The purpose of this paper is to introduce the papers in the current issue and invite comments from the readers of the journal.

Design/methodology/approach

This editorial review is intended to stimulate a discussion about the effect of iterative models of professional development, the meaning of student-centred learning, valid evidence of teachers’ learning through collaborative professional development, teachers’ responses to top-down innovation and the cultural script of teaching, all of which are focal in the texts published in Issue 6.3 of the journal.

Findings

The boundaries between lesson and learning studies, top-down and bottom-up innovations, teacher learning and teacher participation and cultural scripts are far from distinct and for good reasons.

Originality/value

This editorial review provides an overview of the insights and issues identified by the authors in this issue of the journal.
Reconsidering contact risk and contractual risk management
Authors: Schuhmann Ralph , Eichhorn Bert
Published: May 2017

Purpose

The aim of this paper is to pursue three objectives: to assess the extent to which theoretical concepts and corporate practice are reflecting the contract’s risk management dimensions; to identify ways to make full usage of the contract’s risk dimensions for risk management purposes; to overcome the isolation of the contract caused by its perception as a legal instrument by integrating its handling into the overall corporate management processes.

Design/methodology/approach

Literature is analyzed regarding the contract’s roles as a source of risk and as a risk management device. Based on the relevant findings, it uses the Contractual Management Model to develop a concept that integrates all contract-related risk management processes in an enterprise.

Findings

The paper redefines the term “contract risk” in the light of modern understanding of contract functions and contract purposes. It shows that only Contractual Risk Management theory takes the management capacity of the contract fully into account. A Contractual Risk Management process is suggested which integrates all contract-related corporate management processes and aligns them to the requirements of transaction risk management and enterprise risk management.

Originality/value

The paper may guide executives to optimize corporate risk management processes through a better understanding of the risk potential of contract and of its risk management capacity. It provides a checklist of redefined contract risks as well as a concept that, for the first time, is aligning all contract-related management processes to support the corporate risk management system.
Factors affecting employee performance of PT.Kiyokuni Indonesia
Authors: Pawirosumarto Suharno , Sarjana Purwanto Katijan , Muchtar Muzaffar
Published: May 2017

Purpose

This study aims to examine, analyze and explain the influence of leadership style, motivation and discipline to employee performance simultaneously and partially at PT. Kiyokuni Indonesia.

Design/methodology/approach

The primary data used in this study come from questionnaire on respondents’ motivation, discipline, leadership style and employee performance. From 451 people as the population, 82 respondents who met the criteria as a sample were chosen by using the Slovin formula. The analytical method used is multiple linear regression analysis using SPSS Version 22.

Findings

The results of this study indicate that there is a positive and significant influence simultaneously between leadership style, employee motivation and discipline on employee performance. The results also show that there is a positive and significant influence partially between leadership style, employee motivation and discipline on employee performance. Discipline is the variable of the most powerful influence on employee performance, so it needs special attention.

Originality/value

The respondents of this research work for a company which generates products through the work of hands (manual work) and aims to promote the products in the international market.
A declaration for international relations (based on Islamic Sufi teachings)
Authors: Bidabad Bijan
Published: May 2017

Purpose

Establishing peace, security and discipline for individuals, nations and states in contemporary international order is of the highest importance at the present time. Regularization should be done through approaching natural rights of individuals and also through observing humanistic characteristics and ethics. The aim of this paper is to introduce a legal base to promote international relations.

Design/methodology/approach

A draft for International Relation Declaration based on Islamic Sufi teachings has been compiled, and actually it is an abstract of an extended survey on the subject and opinions in relation to the current international problems.

Findings

This draft has been codified in three main topics of public international law, foreign policy and diplomacy.

Research limitations/implications

To conclude the draft, it should be scrutinized by many scholars in different disciplines, in the next step.

Practical implications

As the mystical characteristics of Sufism and Gnosticism of all religions (Tariqa) are all united and based upon love towards the Creator and consequently towards the creatures of God, these provisions could be agreed upon and put into practice.

Social implications

Delicateness, truthfulness and righteousness of Islamic Sufism, which is the gist of all those elites’ divine messages for thousands of years, one after another, can be of a great help to regulate international relations.

Originality/value

International Law scholars have not looked at this subject matter from the Sufism viewpoint. This paper will shed a light on this point of view from other angles related to the international law such as politics, law and institutions.