bluuebunny/crossref_metadata_2025 huggingface dataset:
More Frequent Surveillance Following Lung Cancer Resection Is Not Associated With Improved Survival
Authors: McMurry Timothy L. , Stukenborg George J. , Kessler Larry G. , Colditz Graham A. , Wong Melisa L. , Francescatti Amanda B. , Jones David R. , Schumacher Jessica R. , Greenberg Caprice C. , Chang George J. , Winchester David P. , McKellar Daniel P. , Kozower Benjamin D.
Published: July 2018

Objective:

To evaluate whether an association exists between the intensity of surveillance following surgical resection for non–small cell lung cancer (NSCLC) and survival.

Background:

Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence.

Methods:

A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models.

Results:

A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86–1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99–1.04); P value 0.43].

Conclusions:

These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.
Reactivation of TAp73 tumor suppressor by protoporphyrin IX, a metabolite of aminolevulinic acid, induces apoptosis in TP53-deficient cancer cells
Authors: Sznarkowska Alicja , Kostecka Anna , Kawiak Anna , Acedo Pilar , Lion Mattia , Inga Alberto , Zawacka-Pankau Joanna
Published: July 2018

Background

The p73 protein is a tumor suppressor that shares structural and functional similarity with p53. p73 is expressed in two major isoforms; the TA isoform that interacts with p53 pathway, thus acting as tumor suppressor and the N-terminal truncated ΔN isoform that inhibits TAp73 and p53 and thus, acts as an oncogene.

Results

By employing a drug repurposing approach, we found that protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid (ALA) applied in photodynamic therapy of cancer, stabilizes TAp73 and activates TAp73-dependent apoptosis in cancer cells lacking p53. The mechanism of TAp73 activation is via disruption of TAp73/MDM2 and TAp73/MDMX interactions and inhibition of TAp73 degradation by ubiquitin ligase Itch.

Conclusion

Our findings may in future contribute to the successful repurposing of PpIX into clinical practice.
Communication: Theoretical Insights from Binding of Neigleria fowleri Cell Division Proteins with Amoebicidal Quassinoids
Authors: Basharat Zarrin , Zaib Shumaila , Yasmin Azra
Published: July 2018

The ameboflagellate Neigleria fowleri, also known as brain eating amoeba is responsible for fatal primary amoebic meningoencephalitis (PAM) infection in humans. Cell division proteins (CDPs) in N. fowleri have been uncharacterized until now, despite their importance in the initiation of cell division and proliferation of the pathogen. Here, we report characterization and structural assembly of eight such proteins associated with division and docking them with anti-amoebic quassinoid compounds. Quassinoids have been implicated as inhibitors of cell proliferation of amoeboid species as well as tumor cells. Here, they were screened computationally to find interaction mechanism as well as binding energies with CDPs of N. fowleri. The identified inhibitors could play a role in prevention of cell division and hence, stop N. fowleri growth and proliferation during infection. This study supports CDPs as a target for anti-amoebic intervention and identifies quassinoid phytochemical compounds as suitable for optimization into a new therapy against N. fowleri.
Enabling population assignment from cancer genomes with SNP2pop
Authors: Huang Qingyao , Baudis Michael
Published: July 2018

For a variety of human malignancies, incidence, treatment efficacy and overall prognosis show considerable variation between different populations and ethnic groups. Disentangling the effects related to particular population backgrounds can help in both understanding cancer biology and in tailoring therapeutic interventions. Because self-reported or inferred patient data can be incomplete or misleading due to migration and genomic admixture, a data-driven ancestry estimation should be preferred. While algorithms to analyze ancestry structure from healthy individuals have been developed, an easy-to-use tool to assign population groups based on genotyping data from SNP profiles is still missing and benchmarking for the validity of population assignment strategy for aberrant cancer genomes was not tested.

We benchmarked the consistency and accuracy of cross-platform population assignment. We also demonstrated its high accuracy to process unaltered as well as cancer genomes. Despite widespread and extensive somatic mutations of cancer profiling data, population assignment consistency between germline and highly mutated samples from cancer patients reached of 97% and 92% for assignment into 5 and 26 populations re-spectively. Comparison of our benchmarked results with self-reported meta-data estimated a matching rate between 88% to 92%. Despite a relatively high matching rate, the ethnicity labels indicated in meta-data are vague compared to the standardized output from our tool.

We have developed a bioinformatics tool to assign the populations from genome profiling data and validated its performance in healthy as well as aberrant cancer genomes. It is ready-to-use for genotyping data from nine commercial SNP array platforms or sequencing data. This tool is effective to scrutinize the population structure in cancer genomes and provides better measure to integrate genotyping data from various platforms instead of self-reported information. It will facilitate research on interplay between ethnicity related genetic background and molecular patterns in cancer entities and disentangling possible hereditary contributions.

The docker image of the tool is provided in DockerHub as “baudisgroup/snp2pop”.
A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system ofDrosophila melanogaster
Authors: Pauls Dennis , Blechschmidt Christine , Frantzmann Felix , Jundi Basil el , Selcho Mareike
Published: July 2018

The modulation of an animal’s behavior through external sensory stimuli, previous experience and its internal state is crucial to survive in a constantly changing environment. In most insects, octopamine (OA) and its precursor tyramine (TA) modulate a variety of physiological processes and behaviors by shifting the organism from a relaxed or dormant condition to a responsive, excited and alerted state. Even though OA/TA neurons of the central brain are described on single cell level inDrosophila melanogaster,the periphery was largely omitted from anatomical studies. Given that OA/TA is involved in behaviors like feeding, flying and locomotion, which highly depend on a variety of peripheral organs, it is necessary to study the peripheral connections of these neurons to get a complete picture of the OA/TA circuitry. We here describe the anatomy of this aminergic system in relation to peripheral tissues of the entire fly. OA/TA neurons arborize onto skeletal muscles all over the body and innervate reproductive organs, the heart, the corpora allata, and sensory neurons in the antenna, wings and halteres underlining their relevance in modulating complex behaviors.
Using taxon resampling to identify species with contrasting phylogenetic signals: an empirical example in Terrabacteria
Authors: Superson Ashley A. , Phelan Doug , Dekovich Allyson , Battistuzzi Fabia U.
Published: July 2018

Motivation

The promise of higher phylogenetic stability through increasing dataset size within Tree of Life (TOL) reconstructions has not been fulfilled, especially for deep nodes. Among the many causes proposed are changes in species composition (taxon sampling) that could influence phylogenetic accuracy of the methods by altering the relative weight of the evolutionary histories of each individual species. This effect would be stronger in clades that are represented by few lineages, which is common in many Prokaryote phyla. Indeed, phyla with fewer taxa showed the most discordance among recent TOL studies. Thus, we implemented an approach to systematically test how the number of taxa and the identity of those taxa among a larger dataset affected the accuracy of phylogenetic reconstruction.

Results

We utilized an empirical dataset of 766 fully-sequenced proteomes for phyla within Terrabacteria as a reference for subsampled datasets that differed in both number of species and composition of species. After evaluating the backbone of trees produced as well as the internal nodes, we found that trees with fewer species were more dissimilar to the tree produced from the full dataset. Further, we found that even within scenarios consisting of the same number of taxa, the species used strongly affected phylogenetic stability. These results hold even when the tree is composed by many phyla and only one of them is being altered. Thus, the effect of taxon sampling in one group does not seem to be buffered by the presence of many other clades, making this issue relevant even to very large datasets. Our results suggest that a systematic evaluation of phylogenetic stability through taxon resampling is advisable even for very large datasets.

Contact

battistu@oakland.edu

Supplementary information

Supplementary text and figures are available on the journal’s website.
Apomixis-related genes identified from a coexpression network inPaspalum notatum, a Neotropical grass
Authors: de Oliveira Fernanda A. , Vigna Bianca B. Z. , da Silva Carla C. , Fávero Alessandra P. , Matta Frederico de P. , Azevedo Ana L. S. , de Souza Anete P.
Published: July 2018

Apomixis is a highly desirable trait in modern agriculture, due to the maintenance of characteristics of the mother plant in the progeny. However, incorporating it into breeding programs requires a deeper knowledge of its regulatory mechanisms.Paspalum notatumis considered a good model for such studies because it exhibits both sexual and apomictic cytotypes, facilitating the performance of comparative approaches. Therefore, we used comparative transcriptomics between contrastingP. notatumcytotypes to identify novel candidate genes involved in the regulation of the expression of this phenotype. We assembled and characterized a transcriptome from leaf and inflorescence from apomictic tetraploids and sexual diploids/tetraploids ofP. notatumaccessions, and then assembled a coexpression network based on pairwise correlation between transcripts expression profiles. We identified genes exclusively expressed in each cytotype and differentially expressed genes between pairs of cytotypes. Gene ontology enrichment analyses were performed for the interpretation of data. Wede novoassembled 114,306 of reference transcripts. 536 novel candidate genes for the control of apomixis were detected through statistical analyses of expression data, contains in this set, the interactions among genes potentially linked to the apomixis-controlling region, differentially expressed, several genes also already reported in the literature and their neighbors transcriptionally related in the coexpression network. The reference transcriptome obtained in this study represents a robust set of expression data forP. notatum. Additionally, novel candidate genes identified in this work represent a valuable resource for future grass breeding programs.

Author Summary

Clonal mode of reproduction by seeds is termed apomixis, which results from the failure of gamete formation (meiosis) and fertilization in the sexual female reproductive pathway. The manipulation of seeds production genetically identical to the mother plant bears great promise for agricultural applications, however clarification regarding gene interactions involved in reproductive process is needed.Paspalumis considered a model genus for the analysis of apomixis mechanisms. Here, we describe an overall analysis of the expression profiles ofPaspalum notatumtranscripts in response to changes in reproductive mode (sexual to apomictic), which allowed us to identify several candidate apomixis genes. Among these, we found genes potentially associated with the apomixis control region, in addition to genes already described in the literature forPaspalum, which highlights the representativeness of assembled transcriptome. For the first time in the literature, we explored the main biological processes involved in controlling the expression of apomictic reproduction based on co-regulatory networks of candidate apomixis genes.
Genetic and environmental perturbations lead to regulatory decoherence
Authors: Lea Amanda , Subramaniam Meena , Ko Arthur , Lehtimäki Terho , Raitoharju Emma , Kähönen Mika , Seppälä Ilkka , Mononen Nina , Raitakari Olli T. , Ala-Korpela Mika , Pajukanta Päivi , Zaitlen Noah A. , Ayroles Julien F.
Published: July 2018

Correlation among traits is a fundamental feature of biological systems. From morphological characters, to transcriptional or metabolic networks, the correlations we routinely observe between traits reflect a shared regulation that remains poorly understood and difficult to study. To address this problem, we developed a new and flexible approach that allows us to identify factors associated with variation in correlation between individuals. Here, we use data from three large human cohorts to study the effects of genetic variation and environmental perturbation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (namely, infection and disease) lead to a systematic loss of correlation, which we define as ‘decoherence’. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we show that correlation itself is a trait under genetic control: specifically, we mapped and replicated hundreds of ‘correlation QTLs’, which often involve transcription factors or their known target genes. Together, this work furthers our understanding of how and why coordinated biological processes break down, and highlights the role of decoherence in disease emergence.
Glycosylation enzyme mRNA expression in dorsolateral prefrontal cortex of elderly patients with schizophrenia: Evidence for dysregulation of multiple glycosylation pathways
Authors: Mueller Toni M. , Simmons Micah S. , Helix Ashley T. , Haroutunian Vahram , Meador-Woodruff James H.
Published: July 2018

Altered protein post-translational modifications such as glycosylation have become a target of investigation in the pathophysiology of schizophrenia. Disrupted glycosylation associated processes including atypical sphingolipid metabolism, reduced polysialylation of cell adhesion molecules, abnormal proteoglycan expression, and irregular glycan synthesis and branching have also been reported in this disorder. These pathways are regulated by the expression of glycosidases and glycosyltransferases, classes of enzymes which comprise approximately 2% of the genome. Many glycosylation enzymes can participate in multiple glycosylation pathways and dysregulation of enzyme expression could represent a common mechanism leading to a variety of glycan processing deficits in schizophrenia. In matched pairs of elderly schizophrenia and comparison subject (N = 12 pairs) dorsolateral prefrontal cortex, we measured mRNA levels of 84 key glycosylation enzymes by qPCR array. We found dysregulated transcript expression of 36 glycosylation enzymes from 12 functional categories. All of the abnormally expressed enzymes demonstrated increased transcript expression in schizophrenia, and many altered enzymes are known to modify substrates that have been previously implicated in the pathophysiology this illness. These findings suggest that abnormal glycosylation enzyme expression in schizophrenia may contribute to dysregulation of multiple glycosylation pathways, and disruptions of these central cell signaling processes may underlie a variety of deficits in schizophrenia.
Multi-omics analysis of AML cells treated with azacitidine reveals highly variable cell surface proteome remodeling
Authors: Leung Kevin K , Nguyen Aaron , Shi Tao , Tang Lin , Ni Xiaochun , Escoubet Laure , MacBeth Kyle J , DiMartino Jorge , Wells James A
Published: July 2018

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines (KG1a, HL60, HNT34, and AML193), representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome (methylation array), the transcriptome (gene expression array), and the cell surface proteome (glycoprotein capture with SILAC labeling). Untreated AML cell lines showed substantial overlap in their methylomes, transcriptomes, and cell surface proteomes. AZA treatment globally reduced DNA methylation in all cell lines, but changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment in four AML cell lines had diverse effects at the individual gene and protein level, but converged to regulation of metabolism and immune response at the pathway level. Given the heterogeneous response of AZA in the four cell lines at the gene and protein level, we discuss potential therapeutic strategies for combinations with AZA.
The impact of cigarette smoke exposure, and COPD or asthma status on ABC transporter gene expression in human airway epithelial cells
Authors: Aguiar Jennifer A. , Tamminga Andrea , Lobb Briallen , Huff Ryan D. , Nguyen Jenny , Kim Yechan , Dvorkin-Gheva Anna , Stampfli Martin R. , Doxey Andrew C. , Hirota Jeremy A.
Published: July 2018

Rationale

The respiratory mucosa coordinates responses to infections, allergens, and exposures to air pollution. A relatively unexplored aspect of the respiratory mucosa are the expression and function of ATP Binding Cassette (ABC) transporters. ABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters divided into 7 classes (ABCA, ABCB, ABCC, ABCD, ABDE, ABCF, and ABCG). Throughout the human body, ABC transporters regulate cAMP levels, chloride secretion, lipid transport, and anti-oxidant responses. A deeper exploration of the expression patterns of ABC transporters in the respiratory mucosa is warranted to determine their relevance in lung health and disease.

Methods

We used a bioinformatic approach complemented with in vitro experimental methods for validation of candidate ABC transporters. We analyzed the expression profiles of all 48 human ABC transporters in the respiratory mucosa using bronchial epithelial cell gene expression datasets available in NCBI GEO from well-characterized patient populations of healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma. The Calu-3 airway epithelial cell line was used to interrogate selected results using a cigarette smoke extract exposure model.

Results

Using 9 distinct gene-expression datasets of primary human airway epithelial cells, we completed a focused analysis on 48 ABC transporters in samples from healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma. In situ gene expression data demonstrate that ABC transporters are i) variably expressed in epithelial cells from different airway generations (top three expression levels - ABCA5, ABCA13, and ABCC5), ii) regulated by cigarette smoke exposure (ABCA13, ABCB6, ABCC1, and ABCC3), and iii) differentially expressed in individuals with COPD and asthma (ABCA13, ABCC1, ABCC2, ABCC9). An in vitro cell culture model of cigarette smoke exposure was able to recapitulate the in situ changes observed in cigarette smokers for ABCA13 and ABCC1.

Conclusions

Our in situ human gene expression data analysis reveals that ABC transporters are expressed throughout the airway generations in airway epithelial cells and can be modulated by environmental exposures important in chronic respiratory disease (e.g. cigarette smoking) and in individuals with chronic lung diseases (e.g. COPD or asthma). Our work highlights select ABC transporter candidates of interest and a relevant in vitro model that will enable a deeper understanding of the contribution of ABC transporters in the respiratory mucosa in lung health and disease.
Stable sub-complexes observedin situsuggest a modular assembly pathway of the bacterial flagellar motor
Authors: Kaplan Mohammed , Subramanian Poorna , Ghosal Debnath , Oikonomou Catherine M. , Pirbadian Sahand , Starwalt-Lee Ruth , Gralnick Jeffrey A. , El-Naggar Mohamed Y. , Jensen Grant J.
Published: July 2018

The self-assembly of cellular macromolecular machines such as the bacterial flagellar motor requires the spatio-temporal synchronization of gene expression, protein localization and association of a dozen or more unique components. InSalmonellaandEscherichia coli, a sequential, outward assembly mechanism has been proposed for the flagellar motor starting from the inner membrane, with each subsequent component stabilizing the last. Here, using electron cryo-tomography of intactLegionella pneumophila,Pseudomonas aeruginosaandShewanella oneidensiscells, we observe stable outer-membrane-embedded sub-complexes of the flagellar motor. These sub-complexes consist of the periplasmic embellished P- and L-rings, in the absence of other flagellar components, and bend the membrane inward dramatically. Additionally, we also observe independent inner-membrane sub-complexes consisting of the C- and MS-rings and export apparatus. These results suggest an alternate model for flagellar motor assembly in which outer- and inner-membrane-associated sub-complexes form independently and subsequently join, enabling later steps of flagellar production to proceed.
Genetic Diversity Patterns and Domestication Origin of Soybean
Authors: Jeong Soon-Chun , Moon Jung-Kyung , Park Soo-Kwon , Kim Myung-Shin , Lee Kwanghee , Lee Soo Rang , Jeong Namhee , Choi Man Soo , Kim Namshin , Kang Sung-Taeg , Park Euiho
Published: July 2018

Understanding diversity and evolution of a crop is an essential step to implement a strategy to expand its germplasm base for crop improvement research. Samples intensively collected from Korea, which is a small but central region in the distribution geography of soybean, were genotyped to provide sufficient data to underpin genome-wide population genetic questions. After removing natural hybrids and duplicated or redundant accessions, we obtained a non-redundant set comprising 1,957 domesticated and 1,079 wild accessions to perform population structure analyses. Our analysis demonstrates that while wild soybean germplasm will require additional sampling from diverse indigenous areas to expand the germplasm base, the current domesticated soybean germplasm is saturated in terms of genetic diversity. We then showed that our genome-wide polymorphism map enabled us to detect genetic loci underling flower color, seed-coat color, and domestication syndrome. A representative soybean set consisting of 194 accessions were divided into one domesticated subpopulation and four wild subpopulations that could be traced back to their geographic collection areas. Population genomics analyses suggested that the monophyletic group of domesticated soybeans was originated in eastern Japan. The results were further substantiated by a phylogenetic tree constructed from domestication-associated single nucleotide polymorphisms identified in this study.
High-risk human papillomaviruses down-regulate expression of the Ste20 family kinase MST1 to inhibit the Hippo pathway and promote transformation
Authors: Morgan Ethan L. , Patterson Molly R. , Lee Siu Yi , Wasson Christopher W. , Macdonald Andrew
Published: July 2018

Human papillomaviruses (HPV) are a major cause of malignancy worldwide They are the aetiological agent of almost all cervical cancers and an increasing number of head and neck carcinomas. Deregulation of the Hippo pathway component YAP1 has recently been demonstrated to play a role in HPV-mediated cervical cancer, but whether other components of this pathway are implicated in the pathogenesis of this disease remains poorly understood.

The expression level and activation status of critical Hippo pathway components were analysed across multiple cytology samples from patients with cervical disease, as well as HPV positive (HPV+) and HPV negative (HPV-) cervical cancer cell lines using real time qPCR, western blot and immunohistochemistry. In parallel, we assessed the effects of MST1 and MST2 overexpression upon cervical cancer cell proliferation, migration and invasion. Finally, we interrogated the consequences of interrupted MST1 and MST2 function using a targeted small molecule inhibitor in tandem with kinase inactive MST mutants. Our analysis found that expression of the Ste20 kinase MST1 was decreased within both HPV+ primary patient samples and cervical cancer cell lines. This effect was mediated by the virus-coded oncoproteins E6 and E7, which impair MST1 transcription. Reintroduction of MST1, or its paralogue MST2, into HPV positive cervical cancer cells re-activated the Hippo pathway, leading to a reduction in cell proliferation, migration and invasion. Finally, using a small molecule inhibitor of MST1/2 or kinase inactive mutants of either protein, we demonstrated that this effect required the kinase function of MST1/2. Our results reveal that HPV down regulates MST1 expression to inactivate the Hippo pathway and so drive cells towards transformation.
It takes a dimer to tango: Oligomeric small heat-shock proteins dissociate to capture substrate
Authors: Santhanagopalan Indu , Degiacomi Matteo T. , Shepherd Dale A. , Hochberg Georg K.A. , Benesch Justin L.P. , Vierling Elizabeth
Published: July 2018

Small heat-shock proteins (sHsps) are ubiquitous molecular chaperones, and their mutations or altered expression are linked to multiple human disease states. sHsp monomers assemble into large oligomers with dimeric substructure, and the dynamics of sHsp oligomers has led to major questions about the form that captures substrate, a critical aspect of their mechanism of action. We show that substructural dimers of plant dodecameric sHsps, Ta16.9 and homologous Ps18.1, are functional units in the initial encounter with unfolding substrate. We introduced inter-polypeptide disulfide bonds at the two dodecameric interfaces, dimeric and non-dimeric, to restrict how their assemblies can dissociate. When disulfide bonded at the non-dimeric interface, mutants of Ta16.9 and Ps18.1 (TaCT-ACD and PsCT-ACD) were inactive, but when reduced had wild-type-like chaperone activity, demonstrating that dissociation at non-dimeric interfaces is essential for activity. In addition, the size of the TaCT-ACD and PsCT-ACD covalent unit defined a new tetrahedral geometry for these sHsps, different than the Ta16.9 x-ray structure. Importantly, oxidized Tadimer (disulfide bonded at the dimeric interface) showed greatly enhanced ability to protect substrate, indicating that strengthening the dimeric interface increases chaperone efficiency. Size and secondary structure changes with temperature revealed that folded sHsp dimers interact with substrate, and support dimer stability as a determinant of chaperone efficiency. These data yield a model in which sHsp dimers capture substrate prior to assembly into larger, heterogeneous sHSP-substrate complexes for subsequent substrate refolding or degradation, and suggest that tuning the strength of the dimer interface can be used to engineer sHsp chaperone efficiency.
Double Dissociation of Nicotinic α7 and α4/β2 Sub-receptor Agonists for Enhancing Learning and Attentional Filtering of Distraction
Authors: Azimi Maryzeh , Oemisch Mariann , Womelsdorf Thilo
Published: July 2018

Nicotinic acetylcholine receptors (nAChR) modulate attention, memory, and higher executive functioning, but it has remained unclear whether nAChR sub-receptors tap into different neural mechanisms of these functions. We therefore set out to contrast the contributions of selective alpha-7 nAChR and alpha-4/beta-2 nAChR agonists in mediating value learning and attentional filtering of distractors in the nonhuman primate. We found that the alpha-7 nAChR agonist PHA-543613 selectively enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This double dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times. These results suggest nicotinic sub-receptor-specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.
The posterior parietal cortex and subjectively perceived confidence during memory retrieval
Authors: Wynn Syanah C. , Hendriks Marc P. H. , Daselaar Sander M. , Kessels Roy P. C. , Schutter Dennis J. L. G.
Published: July 2018

Functional neuroimaging studies suggest a role for the left angular gyrus (AG) in processes related to memory recognition. However, results of neuropsychological and transcranial magnetic stimulation (TMS) studies have been inconclusive regarding the specific contribution of the AG in recollection, familiarity, and the subjective experience of memory. To obtain further insight into this issue, 20 healthy right-handed volunteers performed a memory task in a single-blind within-subject controlled TMS study. Neuronavigated inhibitory repetitive TMS (rTMS) was applied over the left AG and the vertex in a randomized and counterbalanced order. Prior to rTMS participants were presented with a list of words. After rTMS participants were shown a second list of words and instructed to indicate if the word was already shown prior to rTMS (“old”) or was presented for the first time (“new”). In addition, subjectively perceived memory confidence was assessed. Results showed that recollection was unaffected following inhibitory left AG rTMS. In contrast, rTMS over the left AG improved both familiarity and the subjectively perceived confidence of participants that demonstrated low baseline memory recognition. Our study highlights the importance of taking into account individual differences in experimental designs involving noninvasive brain stimulation.
Gender-related differences in the use of technology in mathematics classrooms
Authors: Abidin Zaenal , Mathrani Anuradha , Hunter Roberta
Published: July 2018

Purpose

The use of technology in education is still seen as a symbol of modernity in Indonesia. Without adequate technological infrastructural support from institutions, teachers develop ways to incorporate technology into their classrooms. The purpose of this paper is to investigate the affective domain in learning mathematics with technology across genders and across two student groups, where in one group the students shared learning devices, while the other group of students used individual devices.

Design/methodology/approach

The study adopts both quantitative and qualitative methods and is based on data collected from five secondary schools in Indonesia.

Findings

The findings reveal attitudinal differences are associated with technology usage in mathematics classrooms. Quantitative measurements across four attitudinal subscales—mathematics motivation, attitudes to the use of technology in mathematics, technological confidence and mathematics confidence—indicate that affordances in technologies influence boys and girls attitudes; while qualitative data share further insights on gender perspectives related to attitudinal differences.

Research limitations/implications

Appropriate pedagogical approaches with equitable access to technologies are important for engaging students in learning mathematics with technology.

Social implications

This empirical study reveals aspects related to student participation with technologies in classrooms, which has important implications for student development.

Originality/value

The study contributes to literature on mathematics education related to the use of learning technologies in secondary schools of a developing country.
Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial
Authors: Hutton EK , Hannah ME , Willan AR , Ross S , Allen AC , Armson BA , Gafni A , Joseph KS , Mangoff K , Ohlsson A , Sanchez JJ , Asztalos EV , Barrett JFR ,   the Twin Birth Study Collaborative Group
Published: July 2018

Objective

Does planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence?

Design

Women between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth.

Setting

The trial took place at 106 centres in 25 countries.

Population

A total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow‐up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group.

Methods

A structured self‐administered questionnaire completed at 2 years postpartum.

Main outcome measures

The primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 years

Results

Women in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47–0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ‐7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes.

Conclusions

Among women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth.

Funding

Canadian Institutes of Health Research (CIHR) (grant no. MCT‐63164).

Tweetable abstract

For women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years.
How interest groups influence public opinion: Arguments matter more than the sources
Authors: DÜR ANDREAS
Published: July 2018

Through what mechanism do interest groups shape public opinion on concrete policies? In this article, three hypotheses are proposed that distinguish between the effect of the arguments conveyed by interest groups and the effect of interest groups as source cues. Two survey experiments on the proposed Transatlantic Trade and Investment Partnership (TIPP) and the 2015 Paris Agreement on climate change allow the testing of these hypotheses. The resulting evidence from several countries shows that, with respect to interest groups’ attempts at shaping public opinion, arguments matter more than their sources. This is so even when accounting for people's trust in the interest groups that serve as source cues and for people's level of information about a policy. The finding that interest groups affect public opinion via arguments rather than as source cues has implications for the literature on elite influence on public opinion and the normative evaluation of interest group activities.
Analytical Method for Pesticides in Avocado and Papaya by Means of Ultra‐High Performance Liquid Chromatography Coupled to a Triple Quadrupole Mass Detector: Validation and Uncertainty Assessment
Authors: Pano‐Farias Norma S. , Ceballos‐Magaña Silvia G. , Jurado Jose M. , Aguayo‐Villarreal Ismael A. , Muñiz‐Valencia Roberto
Published: July 2018

In this work, the uncertainty estimation for the determination of ametryn, carbofuran, atrazine, carbaryl, and methyl parathion in papaya and avocado is presented, along with other validation parameters. The analytical method was developed using Quick, Easy, Cheap, Effective, Rugged, and Safe extraction and ultrahigh performance liquid chromatography coupled to a triple quadrupole mass detector. The method validation showed that the linear correlation coefficients were higher than 0.99 for both fruits. The limits of detection for avocado and papaya were in the range of 0.022 to 0.46 and 0.003 to 0.109 μg/g, respectively. Intermediate precision varied from 5.3% to 13.0% in papaya, and from 4.8% to 20.2% in avocado. Recoveries obtained for each pesticide in both matrices ranged between 61.3% and 119.0%. Matrix effect was calculated for all compounds in both fruits. Finally, the overall uncertainty was lower than 36% for both fruits.

Practical Application

The present analytical method could be used for pesticides determination in different kind of fruits as papaya and avocado and as a practical guide for uncertainty and matrix effect determination.
Researcher perceptions and choices of interview media: the case of accounting research
Authors: Tucker Basil P. , Parker Lee D.
Published: July 2018

This study offers foundational insights into the ways in which perceptions of different interview media—principally, face‐to‐face, telephone and videoconferencing channels of communication—may influence researcher choices and practices. Informed by the reflections of 23 senior accounting researchers, our evidence identifies a duality of practices in the usage of different interviewing media, influenced primarily through the role played by experience, which informs perceptions upon which practices are based. We discuss this duality of practices in terms of information richness theory and channel expansion theory and offer further insights into the factors that influence and shape researchers’ perceptions of the contextual suitability of particular media available to interview‐based accounting research.
Antibiotic resistance and relevance to general dental practice in Australia
Authors: Teoh L , Stewart K , Marino R , McCullough M
Published: July 2018

Antibiotic resistance is a well‐established global public health crisis, with the use and misuse of antibiotics being the principal cause of bacterial resistance. Studies in both Australia and overseas have demonstrated that the dental prescribing of antibiotics is increasing and that dentists tend to prescribe antibiotics unnecessarily and for incorrect clinical indications. Dental practitioners in Australia also prefer to prescribe moderate to broad‐spectrum antibacterial agents and make some inappropriate antibiotic prescribing choices. This review aims to inform dentists about the overall scope and development of bacterial resistance, approaches and challenges to reducing resistance and, ultimately, the role of dental prescribers in practising with optimal antibiotic stewardship.
Spatial but not temporal dung beetle β‐diversity components are scale‐dependent in a mainland–island scenario
Authors: da Silva Pedro Giovâni , Hernández Malva Isabel Medina
Published: July 2018

β‐diversity is key in understanding how ecological communities have been assembled across spatiotemporal scales. Separating β‐diversity into its process‐related components can provide richer insights into biodiversity organization. In this study, we aimed to investigate the spatial and temporal patterns of β‐diversity components in the composition and structure of dung beetle communities. Dung beetles were sampled in 20 Atlantic Forest sites in a mainland–island scenario. We partitioned β‐diversity dissimilarity based on species composition and abundance into turnover and nestedness components, and into balanced variation in abundance and abundance gradient components respectively. The mainland had higher multiple‐site values of spatial turnover and balanced variation in abundance than the island; meanwhile, nestedness‐resultant dissimilarity and abundance gradients had low relative importance, although the latter values were always higher on the island. There was an increase of spatial turnover and balanced variation in abundance with spatial extent, while nestedness‐resultant dissimilarity and abundance gradients were unrelated to the scale. The temporal turnover increased with increasing spatial extents and a different response pattern occurred between mainland and island. Our study provides support for how spatial extents influence both incidence‐based and abundance‐based β‐diversity components and shape metacommunity composition and structure in mainland–island systems.
Capacity building and social marketing promotes healthy lifestyle behaviour in an Australian Aboriginal community
Authors: Berends Lynda , Halliday Rebecca
Published: July 2018

Objective

We explored the effectiveness of a project targeting an Australian Aboriginal community.

Design

A collaborative approach included stakeholder interviews, an intercept survey, observations and Facebook insights.

Setting

Gippsland encompasses 41 557 km2 of Victoria and has an Aboriginal population of around 4000.

Participants

Five stakeholders from local Aboriginal health/sports organisations were interviewed at 6 and 18 months. A total of 49 Aboriginal persons aged 16 years or more, who lived in Gippsland, were surveyed at a community event. Facebook engagement involved 933 people over a 4‐week period.

Main outcome measures

Reach was assessed at 6 and 18 months using Facebook likes and video views. Survey measures addressed campaign awareness, recall and attitudinal and behavioural change.

Results

The project provides organisations with skills development, social media production and online resources promoting sports and community events. Stakeholders and survey respondents valued local content, positive stories and awareness‐raising elements. Two campaigns developed by state and regional organisations were adapted using locally developed social media with campaign messages. After 18 months, there were 2592 video views and 1738 likes. Forty‐seven (69%) of the eligible attendees at the community event completed the survey. Thirty‐three (70%) had seen the campaign; 20 (61%) subsequently thought about changing their behaviour and 13 (39%) changed their behaviour.

Conclusion

The model was mutually beneficial. Partner organisations enabled project access to local events and project staff supported organisational development and event promotion. Social marketing engaged the community and prompted positive behaviour change. Formative work that is undertaken centrally might be useful for organisations to adapt for local campaigns.
To determine the optimal ultrasonographic screening method for rectal/rectosigmoid deep endometriosis: Ultrasound “sliding sign,” transvaginal ultrasound direct visualization or both?
Authors: Reid Shannon , Espada Mercedes , Lu Chuan , Condous George
Published: July 2018

Introduction

The study aim was to evaluate the transvaginal sonography (TVS) “sliding sign” alone, direct visualization of the bowel with TVS, and the combination of both methods (ie “sliding sign” and direct visualization of the bowel), to determine the optimal TVS method for the prediction of rectal/rectosigmoid deep endometriosis (DE).

Material and methods

Multicenter prospective observational study (January 2009‐February 2017). All women underwent TVS to determine whether the “sliding sign” was positive/negative and whether rectal/rectosigmoid DE was present, followed by laparoscopic surgery. The association between a negative TVS “sliding sign” alone and the direct visualization of a rectal/rectosigmoid DE nodule alone during the TVS were correlated with the presence of rectal/rectosigmoid DE at laparoscopy. Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were evaluated. Data were analyzed using Fisher's exact test.

Results

During the recruitment period, 410 consecutive women with suspected endometriosis were included. Complete TVS and laparoscopic surgical outcomes were available for 376 of the women (91.7%). Complete TVS and laparoscopic data were available for 376 women. Of the 376 women 76 (20.2%) had rectal/rectosigmoid DE at laparoscopy. The accuracy, sensitivity, specificity, PPV, NPV, positive and negative LRs for each method to predict bowel DE were: negative “sliding sign”: 87%, 73.7%, 90.3%, 65.9%, 93.1%, 7.62, and 0.29, respectively; direct visualization: 91.0%, 86.8%, 92.3%, 74.2%, 96.5%, 11.3, and 0.14, respectively; combined approach: 90.2%, 69.7%, 95.3%, 79.1%, 92.6%, 14.94, and 0.32, respectively. A negative TVS “sliding sign” was significantly associated with the need for bowel surgery (P < 0.05).

Conclusions

The combination of the TVS “sliding sign” and direct visualization of the bowel during TVS appears to provide the most accurate assessment for the identification of rectal/rectosigmoid DE preoperatively.