bluuebunny/crossref_metadata_2025 huggingface dataset:
cBinderDB: a covalent binding agent database
Authors: Du Jiewen , Yan Xin , Liu Zhihong , Cui Lu , Ding Peng , Tan Xiaoqing , Li Xiuming , Zhou Huihao , Gu Qiong , Xu Jun
Published: December 2016

Motivation

Small molecule drug candidates with attractive toxicity profiles that modulate target proteins through non-covalent interactions are usually favored by scientists and pharmaceutical industry. In the past decades, many non-covalent binding agents have been developed for different diseases. However, an increasing attention has been paid to covalent binding agents in pharmaceutical fields during recent years. Many covalent binding agents entered clinical trials and exerted significant advantages for diseases such as infection, cancers, gastrointestinal disorders, central nervous system or cardiovascular diseases. It has been recognized that covalent binding ligands can be attractive drug candidates. But, there is lack of resource to support covalent ligand discovery.

Results

Hence, we initiated a covalent binder database (cBinderDB). To our best knowledge, it is the first online database that provides information on covalent binding compound structures, chemotypes, targets, covalent binding types and other biological properties. The covalent binding targets are annotated with biological functions, protein family and domains, gene information, modulators and receptor–ligand complex structure. The data in the database were collected from scientific publications by combining a text mining method and manual inspection processes. cBinderDB covers covalent binder’s data up to September 2016.

Availability and Implementation

cBinderDB is freely available at www.rcdd.org.cn/cbinderdb/

Supplementary information

Supplementary data are available at Bioinformatics online.
Occupational HIV Infection in a Research Laboratory With Unknown Mode of Transmission: A Case Report
Authors: Soria Alessandro , Alteri Claudia , Scarlatti Gabriella , Bertoli Ada , Tolazzi Monica , Balestra Emanuela , Bellocchi Maria Concetta , Continenza Fabio , Carioti Luca , Biasin Mara , Trabattoni Daria , Bandera Alessandra , Ceccherini-Silberstein Francesca , Perno Carlo Federico , Gori Andrea
Published: December 2016

A laboratory worker was infected with human immunodeficiency virus (HIV) type 1 in a biosafety level 2 containment facility, without any apparent breach. Through full-genome sequencing and phylogenetic analyses, we could identify the source of infection in a replication-competent clone that unknowingly contaminated a safe experiment. Mode of transmission remains unclear. Caution is warranted when handling HIV-derived constructs.
A hadronic minute-scale GeV flare from quasar 3C 279?
Authors: Petropoulou M. , Nalewajko K. , Hayashida M. , Mastichiadis A.
Published: December 2016

The flat spectrum radio quasar 3C 279 is a known γ-ray variable source that has recently exhibited minute-scale variability at energies >100 MeV. One-zone leptonic models for blazar emission are severely constrained by the short time-scale variability that implies a very compact emission region at a distance of hundreds of Schwarzschild radii from the central black hole. Here, we investigate a hadronic scenario where GeV γ-rays are produced via proton synchrotron radiation. We also take into account the effects of the hadronically initiated electromagnetic cascades (EMC). For a γ-ray emitting region in rough equipartition between particles and kG magnetic fields, located within the broad-line region (BLR), the development of EMC redistributes the γ-ray luminosity to softer energy bands and eventually leads to broad-band spectra that differ from the observed ones. Suppression of EMC and energy equipartition are still possible, if the γ-ray emitting region is located beyond the BLR, is fast moving with Doppler factor (>70) and contains strong magnetic fields (>100 G). Yet, these conditions cannot be easily met in parsec-scale jets, thus disfavouring a proton synchrotron origin of the Fermi-LAT flare.
Stem cell toxicology: a powerful tool to assess pollution effects on human health
Authors: Yao Xinglei , Yin Nuoya , Faiola Francesco
Published: December 2016

Environmental pollution is a global problem; the lack of comprehensive toxicological assessments may lead to increased health risks. To fully understand the health effects of pollution, it is paramount to implement fast, efficient and specific toxicity screening that relies on human models rather than on time-consuming, expensive and often inaccurate tests involving live animals. Human stem cell toxicology represents a valid alternative to traditional toxicity assays because it takes advantage of the ability of stem cells to differentiate into multiple cell types and tissues of the human body. Thus, this branch of toxicology provides a possibility to assess cellular, embryonic, developmental, reproductive and functional toxicity in vitro within a single system highly relevant to human physiology. In this review, we describe the development, performance and future perspectives of stem cell toxicology, with an emphasis on how it can meet the increasing challenges posed by environmental pollution in the modern world.
Global environmental health: an interview with Sally Perreault Darney
Authors: Xu By Li , Zhao Bin
Published: December 2016

Pollution-induced health problems are of concern across the world. In China, the recent and rapid surge of economic development has been associated with public health problems as well as environmental degradation. We recently spoke with Sally Perreault Darney, Ph.D., the Editor-in-Chief of Environmental Health Perspectives (EHP), the foremost journal about environmental health. Published by the National Institute of Environmental Health Sciences (NIEHS), a part of the US National Institutes of Health, this fully open-access journal publishes peer-reviewed research and commentary, as well news and opinion across the many disciplines that contribute to the field of environmental health, including toxicology, epidemiology, risk assessment and exposure science. We wanted to learn her perspectives on the role that research plays in defining and solving environmental health problems in today's world. Dr. Darney holds a Ph.D. in Biomedical Science and enjoyed a productive research career in the US Environmental Protection Agency (EPA)'s Office of Research and Development, before joining NIEHS in 2015.
Dicer-Like 4 Is Involved in Restricting the Systemic Movement of Zucchini yellow mosaic virus in Nicotiana benthamiana
Authors: Cordero Teresa , Cerdán Lidia , Carbonell Alberto , Katsarou Konstantina , Kalantidis Kriton , Daròs José-Antonio
Published: December 2016

Zucchini yellow mosaic virus (ZYMV) induces serious diseases in cucurbits. To create a tool to screen for resistance genes, we cloned a wild ZYMV isolate and inserted the visual marker Rosea1 to obtain recombinant clone ZYMV-Ros1. While in some plant-virus combinations Rosea1 induces accumulation of anthocyanins in infected tissues, ZYMV-Ros1 infection of cucurbits did not lead to detectable anthocyanin accumulation. However, the recombinant virus did induce dark red pigmentation in infected tissues of the model plant Nicotiana benthamiana. In this species, ZYMV-Ros1 multiplied efficiently in local inoculated tissue but only a few progeny particles established infection foci in upper leaves. We used this system to analyze the roles of Dicer-like (DCL) genes, core components of plant antiviral RNA silencing pathways, in ZYMV infection. ZYMV-Ros1 local replication was not significantly affected in single DCL knockdown lines nor in double DCL2/4 and triple DCL2/3/4 knockdown lines. ZYMV-Ros1 systemic accumulation was not affected in knockdown lines DCL1, DCL2, and DCL3. However in DCL4 and also in DCL2/4 and DCL2/3/4 knockdown lines, ZYMV-Ros1 systemic accumulation dramatically increased, which highlights the key role of DCL4 in restricting virus systemic movement. The effect of DCL4 on ZYMV systemic movement was confirmed with a wild-type version of the virus.
Breast cancer: updates and advances in 2016
Authors: Giordano Sara B. , Gradishar William
Published: December 2016

Purpose of review

Approximately 1 in 8 US women (12%) will develop invasive breast cancer over the course of her lifetime. In 2016, an estimated 246,660 new cases of invasive breast cancer are expected to be diagnosed and approximately 40,450 would die as a result of it. The global burden of breast cancer exceeds all other cancers and the incidence is increasing. The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. This review focuses on the recent advances in breast cancer therapy including hormonal treatment of metastatic breast cancer, targeting cyclin-dependent kinases (CDK) 4/6 in breast cancer, updates in targeting human epidermal growth factor receptor 2 (HER2) positive breast cancer, adaptive randomization trial design and cancer genetic risk assessment.

Recent findings

Breast cancer is a heterogeneous disease and targeted therapy is improving the outcomes of women. The use of cyclin-dependent kinase inhibitors (CDK) 4/6 have demonstrated a substantial improvement in progression-free survival in the first line setting of metastatic hormone receptor positive breast cancer. And newer agents directed at HER2 continue to revolutionize HER2-positive breast cancer treatment.

This review highlights the recent updates in breast cancer treatment, new concepts in clinical trial design and provides a current overview of cancer genetic risk assessment.
The Utility of Low-Dose Aripiprazole for the Treatment of Bipolar II and Bipolar NOS Depression
Authors: Kelly Tammas , Lieberman Daniel Z.
Published: December 2016

Background

Despite initial reports of efficacy in bipolar depression, multicenter trials did not show aripiprazole to be better than placebo, possibly because the doses used were too high, leading to lower efficacy and high dropout rates. This study evaluated the effects of low-dose aripiprazole. Extensive clinical experience has suggested that doses beyond 5 mg are rarely efficacious.

Methods

Data were gathered from patients with bipolar II or bipolar not otherwise specified depression using a retrospective chart review. Efficacy was assessed with the Clinical Global Impression-Improvement score. Patients who had at least 2 trials of aripiprazole were included in a retrospective off-on-off-on experimental design. All patients were on other medications when aripiprazole was started. Patients were treated with doses of 1 to 5 mg.

Findings

On average, patients were rated improved or very much improved compared with baseline. Sixteen of 211 patients worsened or experienced no change. Forty-four patients (21%) discontinued due to adverse effects. The group of patients who underwent off-on-off-on trials experienced statistically significant improvement when they started and restarted aripiprazole, and statistically significant worsening when they discontinued it.

Conclusions

When treating bipolar II or bipolar not otherwise specified depression, low doses of aripiprazole, 5 mg or less, may be more effective and better tolerated than higher ones. Clinicians should start treatment with a very low dose and give patients time to respond.
Therapeutic Effects of Nurse Telephone Follow-up for Lung Cancer Patients in Turkey
Authors: Hintistan Sevilay , Nural Nesrin , Cilingir Dilek , Gursoy Ayla
Published: December 2016

Background:

Patients with lung cancer can encounter many difficulties as they adjust to the side effects of chemotherapy treatments.

Objective:

The aim of this study is to determine the therapeutic effects of nurse telephone follow-up for lung cancer patients.

Methods:

In this quasi-experimental study, the sample consisted of 60 patients with lung cancer assigned to an intervention group (n = 30) and a control group (n = 30). The control group participants were sequentially enrolled first and then the intervention group participants were enrolled. The data were collected using the Patient Information Form, Eastern Cooperative Oncology Group Performance Status, the Edmonton Symptom Assessment Scale, and the Functional Living Index–Cancer. The Nursing Care Guide was created by the nurse researchers’ team and given to both the intervention and control groups. Telephone follow-up calls were conducted with intervention patients within the first week after their chemotherapy session. The Kolmogorov-Smirnov, Pearson χ
2, Fisher exact, Mann-Whitney U, and Friedman test and descriptive statistics were used to evaluate the data.

Results:

Patients in the intervention group demonstrated significantly better adjustment to the symptoms secondary to chemotherapy and higher social functioning quality of life scores compared with reported scores in the control group.

Conclusion:

Nurse telephone follow-up can reduce chemotherapy-related symptoms for lung cancer patients and improve participants’ social functioning.

Implications for Practice:

Nurse telephone follow-up is an acceptable and feasible form of patient contact and is a convenient and efficient way to offer patients the support and continuity of care they need.
Considerations for the Selection of Time-Limited Walk Tests Poststroke: A Systematic Review of Test Protocols and Measurement Properties
Authors: Salbach Nancy M. , O'Brien Kelly K. , Brooks Dina , Irvin Emma , Martino Rosemary , Takhar Pam , Chan Sylvia , Howe Jo-Anne
Published: December 2016

Background and Purpose:

Systematic reviews of research evidence describing the quality and methods for administering standardized outcome measures are essential to developing recommendations for their clinical application. The purpose of this systematic review was to synthesize the research literature describing test protocols and measurement properties of time-limited walk tests in people poststroke.

Methods:

Following an electronic search of 7 bibliographic data-bases, 2 authors independently screened titles and abstracts. One author identified eligible articles, and performed quality appraisal and data extraction.

Results:

Of 12 180 records identified, 43 articles were included. Among 5 walk tests described, the 6-minute walk test (6MWT) was most frequently evaluated (n = 36). Only 5 articles included participants in the acute phase (<1 month) poststroke. Within tests, protocols varied. Walkway length and walking aid, but not turning direction, influenced 6MWT performance. Intraclass correlation coefficients for reliability were 0.68 to 0.71 (12MWT) and 0.80 to 1.00 (2-, 3-, 5- and 6MWT). Minimal detectable change values at the 90% confidence level were 11.4 m (2MWT), 24.4 m (5MWT), and 27.7 to 52.1 m (6MWT; n = 6). Moderate-to-strong correlations (≥0.5) between 6MWT distance and balance, motor function, walking speed, mobility, and stair capacity were consistently observed (n = 33). Moderate-to-strong correlations between 5MWT performance and walking speed/independence (n = 1), and between 12MWT performance and balance, motor function, and walking speed (n = 1) were reported.

Discussion and Conclusions:

Strong evidence of the reliability and construct validity of using the 6MWT poststroke exists; studies in the acute phase are lacking. Because protocol variations influence performance, a standardized 6MWT protocol poststroke for use across the care continuum is needed.

Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A150).
Is Fixing Pediatric Nail Bed Injuries With Medical Adhesives as Effective as Suturing?
Authors: Edwards Sarah , Parkinson Leesa
Published: December 2016

Objectives

Nail bed injuries are common in children, with nail bed damage accounting for 15% to 24% of fingertip injuries. Our objective was to see whether medical adhesives, the cyanoacrylates including Histoacryl and Dermabond, could be used to fix nail bed lacerations as opposed to doing a primary repair with sutures, thus potentially being a quicker method for repair in the emergency department for these injuries.

Methods

We conducted a literature review using the search engines MEDLINE, PubMed, Web of Science, and Google Scholar, and the references within these articles were also integrated. All articles in English were searched. Search terms included “nail bed repair,” “nail bed laceration repair,” and “cyanoacrylate.”

Results

A total of 6 articles were found using the previously mentioned search terms. Four articles using 2-octyl cyanoacrylate or Dermabond for the repair of nail bed injuries were found, with 2 additional articles describing the use of Histoacryl—n-butyl-2-cyanoacrylate—for nail injury repairs.

Conclusions

The 6 articles discussed in this article include approximately 118 patients' worth of data including a mix of adult and pediatric patients. Despite the small numbers and variety of types of study, it is encouraging that there are so many positive results. Cryoacrylates such as Dermabond or Histoacryl maybe useful to assist with nail injuries in children. Therefore, we feel that using a medical adhesive is as effective as suturing nail bed injuries in children.
Successful Management of Fulminant Guillain-Barré Syndrome and Its Complications
Authors: Kamei Atsushi , Akasaka Manami , Araya Nami , Ishikawa Ken , Takada Akira , Furukawa Hiromi , Tanifuji Sachiko , Asami Maya , Nasu Yurie , Oyama Kotaro , Chida Shoichi
Published: December 2016

A 3-year-old girl presented with muscle weakness of her limbs and trunk 6 days after developing symptoms of common cold. Two days later, she experienced respiratory arrest with a Glasgow Coma Scale score of 3, necessitating endotracheal intubation. Therefore, she was transferred to our hospital with suspected acute encephalopathy. Although no abnormalities were observed on brain and spinal magnetic resonance imaging and electroencephalography, peripheral nerve conduction velocity tests failed to evoke motor and sensory nerve action potentials. Thus, we gave a diagnosis of fulminant Guillain-Barré syndrome and initiated immunoglobulin therapy. On day 3 of admission, she developed sinus tachycardia that induced circulatory failure and oliguria, which was successfully treated with landiolol. Subsequently, we performed plasmapheresis followed by immunoglobulin and steroid pulse therapies. She was weaned off the mechanical ventilator by day 20 of admission, was ambulatory by day 44, and had completely recovered without any adverse sequelae by day 55. In conclusion, landiolol was effective for treating acute sinus tachycardia–induced circulatory failure and played a key role in saving the life of this patient.
Clear Cell Carcinoma of the Cervix With Choriocarcinomatous Differentiation: Report of an Extremely Rare Phenomenon Associated With Mismatch Repair Protein Abnormality
Authors: Mukonoweshuro Pinias , McCluggage W. Glenn
Published: December 2016

The presence of trophoblastic differentiation or nongestational choriocarcinoma in a carcinoma is rare but has been described in various organs, including in the female genital tract. We report a cervical clear cell carcinoma admixed with a component of choriocarcinoma in a 52-year-old woman, only the second report of this combination in the literature. Immunohistochemically, the tumor exhibited isolated loss of staining with the mismatch repair protein MSH6. We review the literature on trophoblastic differentiation in cervical carcinoma.
Strain rate sensitivity of the tensile strength of two silicon carbides: experimental evidence and micromechanical modelling
Authors: Zinszner Jean-Luc , Erzar Benjamin , Forquin Pascal
Published: December 2016

Ceramic materials are commonly used to design multi-layer armour systems thanks to their favourable physical and mechanical properties. However, during an impact event, fragmentation of the ceramic plate inevitably occurs due to its inherent brittleness under tensile loading. Consequently, an accurate model of the fragmentation process is necessary in order to achieve an optimum design for a desired armour configuration. In this work, shockless spalling tests have been performed on two silicon carbide grades at strain rates ranging from 103to 104 s−1using a high-pulsed power generator. These spalling tests characterize the tensile strength strain rate sensitivity of each ceramic grade. The microstructural properties of the ceramics appear to play an important role on the strain rate sensitivity and on the dynamic tensile strength. Moreover, this experimental configuration allows for recovering damaged, but unbroken specimens, giving unique insight on the fragmentation process initiated in the ceramics. All the collected data have been compared with corresponding results of numerical simulations performed using the Denoual–Forquin–Hild anisotropic damage model. Good agreement is observed between numerical simulations and experimental data in terms of free surface velocity, size and location of the damaged zones along with crack density in these damaged zones.

This article is part of the themed issue ‘Experimental testing and modelling of brittle materials at high strain rates’.
Use of simulated experiments for material characterization of brittle materials subjected to high strain rate dynamic tension
Authors: Lukić Bratislav , Saletti Dominique , Forquin Pascal
Published: December 2016

Rapid progress in ultra-high-speed imaging has allowed material properties to be studied at high strain rates by applying full-field measurements and inverse identification methods. Nevertheless, the sensitivity of these techniques still requires a better understanding, since various extrinsic factors present during an actual experiment make it difficult to separate different sources of errors that can significantly affect the quality of the identified results. This study presents a methodology using simulated experiments to investigate the accuracy of the so-called spalling technique (used to study tensile properties of concrete subjected to high strain rates) by numerically simulating the entire identification process. The experimental technique uses the virtual fields method and the grid method. The methodology consists of reproducing the recording process of an ultra-high-speed camera by generating sequences of synthetically deformed images of a sample surface, which are then analysed using the standard tools. The investigation of the uncertainty of the identified parameters, such as Young's modulus along with the stress–strain constitutive response, is addressed by introducing the most significant user-dependent parameters (i.e. acquisition speed, camera dynamic range, grid sampling, blurring), proving that the used technique can be an effective tool for error investigation.

This article is part of the themed issue ‘Experimental testing and modelling of brittle materials at high strain rates’.
Hypervelocity impacts into porous graphite: experiments and simulations
Authors: Hébert D. , Seisson G. , Rullier J.-L. , Bertron I. , Hallo L. , Chevalier J.-M. , Thessieux C. , Guillet F. , Boustie M. , Berthe L.
Published: December 2016

We present experiments and numerical simulations of hypervelocity impacts of 0.5 mm steel spheres into graphite, for velocities ranging between 1100 and 4500 m s
−1
. Experiments have evidenced that, after a particular striking velocity, depth of penetration no longer increases but decreases. Moreover, the projectile is observed to be trapped below the crater surface. Using numerical simulations, we show how this experimental result can be related to both materials, yield strength. A Johnson–Cook model is developed for the steel projectile, based on the literature data. A simple model is proposed for the graphite yield strength, including a piecewise pressure dependence of the Drucker–Prager form, which coefficients have been chosen to reproduce the projectile penetration depth. Comparisons between experiments and simulations are presented and discussed. The damage properties of both materials are also considered, by using a threshold on the first principal stress as a tensile failure criterion. An additional compressive failure model is also used for graphite when the equivalent strain reaches a maximum value. We show that the experimental crater diameter is directly related to the graphite spall strength. Uncertainties on the target yield stress and failure strength are estimated.

This article is part of the themed issue ‘Experimental testing and modelling of brittle materials at high strain rates’.
Effects of strain rate and surface cracks on the mechanical behaviour of Balmoral Red granite
Authors: Mardoukhi Ahmad , Mardoukhi Yousof , Hokka Mikko , Kuokkala Veli-Tapani
Published: December 2016

This work presents a systematic study on the effects of strain rate and surface cracks on the mechanical properties and behaviour of Balmoral Red granite. The tensile behaviour of the rock was studied at low and high strain rates using Brazilian disc samples. Heat shocks were used to produce samples with different amounts of surface cracks. The surface crack patterns were analysed using optical microscopy, and the complexity of the patterns was quantified by calculating the fractal dimensions of the patterns. The strength of the rock clearly drops as a function of increasing fractal dimensions in the studied strain rate range. However, the dynamic strength of the rock drops significantly faster than the quasi-static strength, and, because of this, also the strain rate sensitivity of the rock decreases with increasing fractal dimensions. This can be explained by the fracture behaviour and fragmentation during the dynamic loading, which is more strongly affected by the heat shock than the fragmentation at low strain rates.

This article is part of the themed issue ‘Experimental testing and modelling of brittle materials at high strain rates’.
An improved computational constitutive model for glass
Authors: Holmquist Timothy J. , Johnson Gordon R. , Gerlach Charles A.
Published: December 2016

In 2011, Holmquist and Johnson presented a model for glass subjected to large strains, high strain rates and high pressures. It was later shown that this model produced solutions that were severely mesh dependent, converging to a solution that was much too strong. This article presents an improved model for glass that uses a new approach to represent the interior and surface strength that is significantly less mesh dependent. This new formulation allows for the laboratory data to be accurately represented (including the high tensile strength observed in plate-impact spall experiments) and produces converged solutions that are in good agreement with ballistic data. The model also includes two new features: one that decouples the damage model from the strength model, providing more flexibility in defining the onset of permanent deformation; the other provides for a variable shear modulus that is dependent on the pressure. This article presents a review of the original model, a description of the improved model and a comparison of computed and experimental results for several sets of ballistic data. Of special interest are computed and experimental results for two impacts onto a single target, and the ability to compute the damage velocity in agreement with experiment data.

This article is part of the themed issue ‘Experimental testing and modelling of brittle materials at high strain rates’.
In
vitro antifungal susceptibilities of Candida species to liposomal amphotericin B, determined using CLSI broth microdilution, and amphotericin B deoxycholate, measured using the Etest
Authors: Lovero Grazia , Giglio Osvalda De , Rutigliano Serafina , Diella Giusy , Caggiano Giuseppina , Montagna Maria Teresa
Published: December 2016

The antifungal susceptibilities of 598 isolates of Candida spp. (bloodstream and other sterile sites) to liposomal amphotericin B (L-AmB) versus amphotericin B (AmB) were determined. MICs were calculated using the Clinical and Laboratory Standards Institute broth microdilution (M27-A3) method for L-AmB and the Etest method for AmB. The MIC50/MIC90 (µg ml−1) values for L-AmB broth microdilution and AmB Etest were 0.25/1 and 0.19/0.5, respectively. The overall essential agreement (±2 dilutions) was 91.5 %, ranging from 37.5 % (Candida lusitaniae) to 100 % (Candida glabrata and Candida krusei). Categorical agreement between the two methods was categorized based on a previously published breakpoint (susceptible/resistant MIC cut-off of 1 µg ml−1). The overall categorical agreement at the 48 h reading was 97.3 %, ranging from 72.7 % (C. krusei) to 100 % (Candida albicans). Major and very major discrepancies occurred in 2.3 and 0.3 %, respectively. Spearman’s ρ was 0.48 (P<0.0001). These results demonstrate the utility of the AmB Etest as a surrogate marker to predict the sensibility and resistance of Candida spp. to L-AmB and thus to support its use in antifungal treatment.
Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer
Authors: Gonçalves Emanuel , Fragoulis Athanassios , Garcia-Alonso Luz , Cramer Thorsten , Saez-Rodriguez Julio , Beltrao Pedro
Published: December 2016

Chromosomal rearrangements, despite being detrimental, are ubiquitous in cancer and often act as driver events. The effect of copy number variations (CNVs) on the cellular proteome of tumours is poorly understood. Therefore, we have analysed recently generated proteogenomic data-sets on 282 tumour samples to investigate the impact of CNVs in the proteome of these cells. We found that CNVs are post-transcriptionally attenuated in 23-33% of proteins with an enrichment for protein complexes. Complex subunits are highly co-regulated and some act as rate-limiting steps of complex assembly, indirectly controlling the abundance of other complex members. We identified 48 such regulatory interactions and experimentally validated AP3B1 and GTF2E2 as controlling subunits. Lastly, we found that a gene-signature of protein attenuation is associated with increased resistance to chaperone and proteasome inhibitors. This study highlights the importance of post-transcriptional mechanisms in cancer which allow cells to cope with their altered genomes.
Protein phosphatase 1 down regulates ZYG-1 levels to limit centriole duplication
Authors: Peel Nina , Iyer Jyoti , Naik Anar , Dougherty Michael P , Decker Markus , O’Connell Kevin F
Published: December 2016

In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. TheC. eleganshomolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2szy-2and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation ofszy-2orsds-22can rescue the loss of centriole duplication associated with azyg-1hypomorphic allele. Suppression is achieved through an increase in ZYG-1 levels, and our data indicate that PP1 normally regulates ZYG-1 through a post-translational mechanism. While moderate inhibition of PP1 activity can restore centriole duplication to azyg-1mutant, strong inhibition of PP1 in a wild-type background leads to centriole amplification via the production of more than one daughter centriole. Our results thus define a new pathway that limits the number of daughter centrioles produced each cycle.

Author Summary

The centrosomes are responsible for organizing the mitotic spindle a microtubule-based structure that centers, then segregates, the chromosomes during cell division. When a cell divides it normally possesses two centrosomes, allowing it to build a bipolar spindle and accurately segregate the chromosomes to two daughter cells. Appropriate control of centrosome number is therefore crucial to maintaining genome stability. Centrosome number is largely controlled by their regulated duplication. In particular, the protein Plk4, which is essential for duplication, must be strictly limited as an overabundance leads to excess centrosome duplication. We have identified protein phosphatase 1 as a critical regulator of theC. elegansPlk4 homolog (known as ZYG-1). When protein phosphatase 1 is down-regulated, ZYG-1 levels increase leading to centrosome amplification. Thus our work identifies a novel mechanism that limits centrosome duplication.
Genetic overlap between educational attainment, schizophrenia and autism
Authors: Warrier Varun , Bethlehem Richard AI , Geschwind Daniel H , Baron-Cohen Simon
Published: December 2016

Importance

The genetic relationship between cognition, autism, and schizophrenia is complex. It is unclear how genes that contribute to cognition also contribute to risk for autism and schizophrenia.

Objective

To investigate the interaction between genes related to cognition (measured via proxy through educational attainment, which we call ‘edu genes’) and genes/biological pathways that are atypical in autism and schizophrenia.

Design

Genetic correlation and enrichment analysis were conducted to identify the interaction between edu genes and risk genes and biological pathways for autism or schizophrenia.

Results

First, edu genes are enriched in a specific developmental co-expression module that is also enriched for high confidence autism risk genes. Second, modules enriched for genes that are dysregulated in autism and schizophrenia are also enriched for edu genes. Finally, genes that overlap between the two above modules and educational attainment are significantly enriched for genes that flank human accelerated regions, suggesting increased positive selection for the overlapping gene sets.

Conclusion

Our results identify distinct co-expression modules where risk genes for the two psychiatric conditions interact with edu genes. This suggests specific pathways that contribute to both cognitive deficits and cognitive talents, in individuals with schizophrenia or autism.

Key Points

Question

How do genes for educational attainment interact with risk genes for autism and schizophrenia?

Findings

We show that genes for educational attainment (edu genes) are significantly likely to be mutated in autism and intellectual disability. We further show that edu genes also interact with co-expression modules that are associated with autism or schizophrenia and are enriched for differentially expressed genes in autism or schizophrenia. Finally, we identify that the enrichment between risk genes for autism and schizophrenia and human accelerated regions are driven, in part, by their overlap with edu genes.

Meaning

Edu genes interact with schizophrenia and autism risk genes in specific pathways, contributing to both cognitive deficits and talents.
Quantitative characterization of the X-ray beam at the Australian Synchrotron Imaging and Medical Beamline (IMBL)
Authors: Stevenson Andrew W. , Crosbie Jeffrey C. , Hall Christopher J. , Häusermann Daniel , Livingstone Jayde , Lye Jessica E.
Published: December 2016

A critical early phase for any synchrotron beamline involves detailed testing, characterization and commissioning; this is especially true of a beamline as ambitious and complex as the Imaging & Medical Beamline (IMBL) at the Australian Synchrotron. IMBL staff and expert users have been performing precise experiments aimed at quantitative characterization of the primary polychromatic and monochromatic X-ray beams, with particular emphasis placed on the wiggler insertion devices (IDs), the primary-slit system and any in vacuo and ex vacuo filters. The findings from these studies will be described herein. These results will benefit IMBL and other users in the future, especially those for whom detailed knowledge of the X-ray beam spectrum (or `quality') and flux density is important. This information is critical for radiotherapy and radiobiology users, who ultimately need to know (to better than 5%) what X-ray dose or dose rate is being delivered to their samples. Various correction factors associated with ionization-chamber (IC) dosimetry have been accounted for, e.g. ion recombination, electron-loss effects. A new and innovative approach has been developed in this regard, which can provide confirmation of key parameter values such as the magnetic field in the wiggler and the effective thickness of key filters. IMBL commenced operation in December 2008 with an Advanced Photon Source (APS) wiggler as the (interim) ID. A superconducting multi-pole wiggler was installed and operational in January 2013. Results are obtained for both of these IDs and useful comparisons are made. A comprehensive model of the IMBL has been developed, embodied in a new computer program named spec.exe, which has been validated against a variety of experimental measurements. Having demonstrated the reliability and robustness of the model, it is then possible to use it in a practical and predictive manner. It is hoped that spec.exe will prove to be a useful resource for synchrotron science in general, and for hard X-ray beamlines, whether they are based on bending magnets or insertion devices, in particular. In due course, it is planned to make spec.exe freely available to other synchrotron scientists.
(E)-1-(4-Methoxyphenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one
Authors: Sunitha V. M. , Naveen S. , Dileep Kumar A. , Ajay Kumar K. , Lokanath N. K. , Manivannan V. , Manjunath H. R.
Published: December 2016

In the title chalcone derivative, C19H20O5, the dihedral angle between the planes of the benzene rings is 3.97 (8)°. In the monosubstituted ring, the methoxy C atom is almost coplanar with the ring [deviation = 0.016 (3) Å]. In the trisubstituted ring, the C atoms of theortho,metaandparamethoxy sustituents deviate by −0.030 (2), 1.127 (2) and −0.052 (2) Å, respectively. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, formingC(9) chains propagating along [010].
(5Z)-3-(2-Oxopropyl)-5-(3,4,5-trimethoxybenzylidene)-1,3-thiazolidine-2,4-dione
Authors: Mague Joel T. , Mohamed Shaaban K. , Akkurt Mehmet , El-Kashef Hussein , Lebegue Nicolas , Albayati Mustafa R.
Published: December 2016

In the crystal of the title molecule, C16H17NO6S, there are three sets of intermolecular C—H...O hydrogen bonds, as well as two sets of intermolecular C—H...π(ring) interactions. In addition, the thiazolidene rings participate in offset π–π stacking interactions [centroid–centroid distance = 3.685 (1) Å]. These generate small channels running parallel to theaaxis with approximate cross-sections of 3.7 × 8.1 Å.
(E)-1-(5-Chlorothiophen-2-yl)-3-(2,4-dimethylphenyl)prop-2-en-1-one
Authors: Naveen S. , Prabhudeva M. G. , Ajay Kumar K. , Lokanath N. K. , Abdoh Muneer
Published: December 2016

In the title compound, C15H13ClOS, the olefinic double bond adopts anEconfiguration. The molecule is nearly planar, as seen by the dihedral angle of 9.07 (8)° between the thiophene and phenyl rings. Thetransconfiguration of the C=C double bond in the central enone group is confirmed by the C—C=C—C torsion angle of 177.6 (2)°. In the crystal, molecules are linked by weak C—H...O and C—H...S hydrogen bonds, forming chains propagating along thecaxis.
Sea fish fraud? A confirmation of Gadoid species food labelling
Authors: Kyrova Veronika , Surmanova Pavla , Ostry Vladimir , Rehurkova Irena , Ruprich Jiri , Jechova Marie
Published: December 2016

Purpose

Gadoid fish and hake are the species of fishes most frequently imported to the Czech Republic. The purpose of this paper, cross-country hygiene study, is to determine sea fish fraud labelling on the Czech market and catering.

Design/methodology/approach

In total, 57 samples of commercial Gadoid fish product from different manufacturers, distributors and catering facilities were gathered. Gadidae family, hake (Merlucciusspp. Raf.), saithe (Pollachius virensL.), Atlantic cod (Gadus morhuaL.), Alaska pollock (Theragra chalcogrammaPall.), were detected in fish meat, fish products and fish meals by the qualitative PCR method.

Findings

In total, 47 samples were labelled as a Gadoid fish, which were confirmed in 43 cases. Six samples were labelled as a hake and were confirmed in five samples. Four samples were labelled as a fish fillets. Three samples of fish fillets were identified as a hake and one sample was detected as a mixture of Alaska pollock and Atlantic cod.

Social implications

In recent years, due to increasing interest from consumers in the sea fish meat market, accurate Identification of fish species has become more important. The mislabelling of sea fish species, whether intentional or not, was on observed on the Czech market and in catering facilities. Economic factors influence the accuracy of labelling of fish meat, which is a concern as mislabelling can threaten public health.

Originality/value

The study was concentrated on the monitoring of hygiene and quality of food products and catering facilities. This study provides greater awareness of the condition and quality of food on the market and to the extent of fraudulent practices amongst dealers and producers.
Food integrity: a market-based solution
Authors: Wang Chao-shih , Van Fleet David D. , Mishra Ashok K.
Published: December 2016

Purpose

The purpose of this paper is to proffer an alternative conceptualization of food integrity and a market-based food integrity intelligence system.

Design/methodology/approach

Food fraud is interpreted as a symptom of asymmetric knowledge. Consumer collaboration for knowledge exchange and diffusion of innovation (KEDI) safeguards food markets. The concept of communicative action is applied to conceptualize and analyze key elements for designing a collaborative food integrity intelligence system.

Findings

The model of market-based KEDI consists of three dimensions: intelligence flows, organization memory, and social sensitivities. Decentralized control is crucial to effect system innovation.

Originality/value

The paper integrates managerial, marketing, and economic approaches and develops a model for managing food integrity intelligence.
Food scares: a comprehensive categorisation
Authors: Whitworth Elizabeth , Druckman Angela , Woodward Amy
Published: December 2016

Purpose

The purpose of this paper is to describe the development of a comprehensive categorisation of food scares.

Design/methodology/approach

Following an initial desktop study, the categorisation was developed collaboratively with industry experts through a workshop and series of semi-structured interviews.

Findings

The new categorisation developed is in Venn diagram format allowing overlapping categories. It is organised around the two major types of contamination (biological, and chemical/physical contaminants) and the two major causes of contamination (wilful deception, and transparency and awareness issues).

Practical implications

The long and complex supply chains characteristic of current food production systems have resulted in a rising number of food scares. There is thus an increased emphasis on developing strategies to reduce both the number of incidents of food scares, and their associated economic, social and environmental impacts. The new categorisation developed in this study enables experts to address categories of food scares. Inclusion of the cause of contamination is particularly important as the method through which contamination occurs is key in devising food scare prevention strategies.

Originality/value

The new categorisation, unlike previous categorisations, enables food scares to fall into multiple categories, as appropriate. Also, again in contrast to previous categorisations, it takes into account not only the physical problem of a food scare but also the mechanism through which it arises.
Study on FT-MIR spectra of ghee (anhydrous milk fat)
Authors: Antony Bency , Sharma Saurabh , Mehta Bhavbhuti Manojbhai , Ratnam K. , Aparnathi K.D.
Published: December 2016

Purpose

Ghee, anhydrous milk fat, is chemically highly complex in nature. The authentication and characterization of edible fats and oils by routine chemical methods are highly laborious and time consuming. Fourier transform-mid-infrared (FT-MIR) spectroscopy has emerged as a predominant analytical tool in the study of edible fats/oils. However, sufficient attention has not been paid so far to spectral characterization of milk fat obtained from cow and buffalo milk. The purpose of this paper is to fill this void.

Design/methodology/approach

Ghee samples were prepared from cow and buffalo milk by the direct cream method. From each type of milk (cow and buffalo), 35 samples of ghee were prepared; thus, in total, 70 samples of ghee were obtained for the study. For assigning absorption bands in the IR spectrum, spectra of cow and buffalo ghee samples were acquired in the MIR region (4,000-650 cm−1).

Findings

In FT-MIR spectra of ghee, 14 peaks were obtained at different positions and with varying intensities. They were at 3,005, 2,922, 2,853, 1,744, 1,466, 1,418, 1,377, 1,236, 1,161, 1,114, 1,098, 966, 870 and 721 cm−1 for cow and buffalo ghee with almost equal intensity of absorption.

Practical implications

The finding of this study will be useful for characterization and authentication of ghee.

Originality/value

Application of IR spectral bands of ghee in the MIR region using a FT-infrared spectrometer to monitor the quality of ghee is suggested.
A conceptual understanding of criminality and integrity challenges in food supply chains
Authors: Fassam Liam , Dani Samir
Published: December 2016

Purpose

Business, consumers and governmental organisations are harbouring a growing need to gain an appreciation of behaviours connected to food criminality. In order to acquire a cross-functional understanding of these thematic areas (crime and fraud) the mapping of existing research is needed. The paper aims to discuss these issues.

Design/methodology/approach

This paper contributes to the process of knowledge understanding, by systematically reviewing literature to provide an analysis of the current body of business knowledge against the thematic criterion of “supply chain food crime” and “supply chain food fraud”. The analysis derives themes from the literature and maps this across the eight pillars underpinning the UK Government paper on food supply chain resilience.

Findings

A distinct gap lies with the eight pillars of food supply chain resilience, business interest into supply chain criminality and academic research into the field. There are noteworthy gaps when the literature is analysed to that of the UK Government report.

Research limitations/implications

The limitation of the study was its focus on business-only journals; a plethora of literature resides in the science field (e.g. testing) that has not made its way to business text.

Practical implications

Drawing inference between business research and the government report, clear identification and tangible research areas can be immediately exploited to align cross-functional thinking.

Social implications

The gap of consumer is not as yet addressed in this field, this research contributes originally to this gap and the need to address the same for societal benefit.

Originality/value

The paper concentrates on the metrics know to contribute to “food crime” and “food fraud” and deviating views of academic vs non-academic literature. In conclusion the paper identifies thematic areas for further research and presents a conceptual framework of food supply chain resilience.