bluuebunny/crossref_metadata_2025 huggingface dataset:
Dorsomedial prefrontal cortex activity during learning discriminates response to Cognitive Behavioural Therapy in depression
Authors: Queirazza Filippo , Fouragnan Elsa , Steele J. Douglas , Cavanagh Jonathan , Philiastides Marios G.
Published: November 2017

BACKGROUND

Cognitive behavioural therapy (CBT) is an effective evidence based treatment for depression. At present there is no reliable predictor of CBT in depression. Although the key to successful CBT in depression lies in altering maladaptive information processing, no previous imaging study has probed predictors of CBT response using pre-treatment neural encoding of information processing. METHODS: Using functional magnetic resonance imaging we scanned 37 unmedicated depressed subjects before and after completing computerised CBT (cCBT). We model the trial-by-trial appraisal of feedback information during a probabilistic learning task by means of a dynamic learning rate. To discriminate response to cCBT we capitalise on the pre-treatment blood oxygen level dependent (BOLD) activity encoding the dynamic learning rate as a function of feedback congruence and valence. Additionally, we probe between-group differences in the learning style encoded in the model’s parameters.

RESULTS

We show BOLD activity in the dorsomedial prefrontal cortex (dmPFC) to be encoding the dynamic learning rate. Crucially, responders exhibit greater BOLD activity in the dmPFC during incongruent negative trials but lower BOLD activity during congruent negative trials than non-responders. Additionally, on between-group comparisons of model’s parameter estimates we show responders take relatively greater account of previous feedback history and make comparatively smaller adjustments to the learning rate as a result of outcome surprisingness.

CONCLUSIONS

Our findings provide novel and important insights into the cognitive mechanisms underpinning response to cCBT and lend support to the feasibility and validity of neurocomputational approaches to treatment prediction research in psychiatry.
Mapping the phenotypic repertoire of the cytoplasmic 2-Cys peroxiredoxin – thioredoxin system. 1. Understanding commonalities and differences among cell types
Authors: Selvaggio Gianluca , Coelho Pedro M. B. M. , Salvador Armindo
Published: November 2017

The system (PTTRS) formed by typical 2-Cys peroxiredoxins (Prx), thioredoxin (Trx), Trx reductase (TrxR), and sulfiredoxin (Srx) is central in antioxidant protection and redox signaling in the cytoplasm of eukaryotic cells. Understanding how the PTTRS integrates these functions requires tracing phenotypes to molecular properties, which is non-trivial. Here we analyze this problem based on a model that captures the PTTRS’ conserved features. We have mapped the conditions that generate each distinct response to H2O2 supply rates (νsup), and estimated the parameters for thirteen human cell types and for Saccharomyces cerevisiae. The resulting composition-to-phenotype map yielded the following experimentally testable predictions. The PTTRS permits many distinct responses including ultra-sensitivity and hysteresis. However, nearly all tumor cell lines showed a similar response characterized by limited Trx-S- depletion and a substantial but self-limited gradual accumulation of hyperoxidized Prx at high νsup. This similarity ensues from strong correlations between the TrxR, Srx and Prx activities over cell lines, which contribute to maintain the Prx-SS reduction capacity in slight excess over the maximal steady state Prx-SS production. In turn, in erythrocytes, hepatocytes and HepG2 cells high νsup depletes Trx-S- and oxidizes Prx mainly to Prx-SS. In all nucleated human cells the Prx-SS reduction capacity defined a threshold separating two different regimes. At sub-threshold νsup cytoplasmic H2O2 is determined by Prx, nM-range and spatially localized, whereas at supra-threshold νsup it is determined by much less active alternative sinks and μM-range throughout the cytoplasm. The yeast shows a distinct response where the Prx Tsa1 accumulates in sulfenate form at high νsup. This is mainly due to an exceptional stability of Tsa1’s sulfenate.

The implications of these findings for thiol redox regulation and cell physiology are discussed. All estimates were thoroughly documented and provided, together with analytical approximations for system properties, as a resource for quantitative redox biology.

Abbreviations

ASK1, apoptosis signal-regulating kinase 1; Cat, catalase; GSH, glutathione; GPx1, glutathione peroxidase 1; Grx, glutaredoxin; KEAP1, Kelch-like ECH-associated protein 1; NRF2, nuclear factor erythroid 2-related factor 2; Prx, typical 2-Cys peroxiredoxin; PTTRS, peroxiredoxin / thioredoxin / thioredoxin reductase system; Srx, sulfiredoxin; Trx, thioredoxin; TrxR, thioredoxin reductase.
Prevalence of loss-of-function alleles does not correlate with lifetime fecundity and other life-history traits in metazoans
Authors: Bezmenova Aleksandra V. , Bazykin Georgii A. , Kondrashov Alexey S.
Published: November 2017

Natural selection is possible only because all species produce more offspring than what is needed to maintain the population. Still, the lifetime number of offspring varies widely across species. One can expect natural selection to be stronger in high-fecundity species. We analyzed the prevalence of loss-of-function alleles in 32 metazoan species and have found that, in contrast to this expectation, the strength of negative selection does not correlate with lifetime fecundity, as well as with other life-history traits. Perhaps, higher random mortality in high-fecundity species negates the effect of increased opportunity for selection.
Is chaos making a difference? Synchronization transitions in chaotic and nonchaotic neuronal networks
Authors: Xu Kesheng , Maidana Jean Paul , Castro Samy , Orio Patricio
Published: November 2017

Chaotic dynamics of neural oscillations has been shown at the single neuron and network levels, both in experimental data and numerical simulations. Theoretical studies over the last twenty years have demonstrated an underlying role of chaos in neural systems. Nevertheless, whether chaotic neural oscillators make a significant contribution to relevant network behavior and whether the dynamical richness of neural networks are sensitive to the dynamics of isolated neurons, still remain open questions. We investigated transition dynamics of a medium-sized heterogeneous neural network of neurons connected by electrical coupling in a small world topology. We make use of an oscillatory neuron model (HB+Ih) that exhibits either chaotic or non-chaotic behavior at different combinations of conductance parameters. Measuring order parameter as a measure of synchrony, we find that the heterogeneity of firing rate and types of firing patterns make a greater contribution than chaos to the steepness of synchronization transition curve. We also show that chaotic dynamics of the isolated neurons do not always make a visible difference in process of network synchronization transitions. Moreover, the macroscopic chaos is observed regardless of the dynamics nature of the neurons. However, performing a Functional Connectivity Dynamics analysis, we show that chaotic nodes can promote what is known as the multi-stable behavior, where the network dynamically switches between a number of different semi-synchronized, metastable states.
C-terminal truncation of Pik3r1 in mice models human lipodystrophic insulin resistance uncoupled from dyslipidemia
Authors: Kwok Albert , Zvetkova Ilona , Virtue Sam , Huang-Doran Isabel , Tomlinson Patsy , Bulger David A. , Hart Daniel , Knox Rachel , Franks Stephen , Voshol Peter , Vidal-Puig Antonio , Sferruzzi-Perri Amanda N. , Jensen Jørgen , O’Rahilly Stephen , Semple Robert K
Published: November 2017

Heterodimeric class IA phosphatidylinositol-3-kinases (PI3K) transduce signals from many receptor tyrosine kinases including the insulin receptor. PI3K recruitment to phosphotyrosines is mediated byPik3r1gene products including the most intensely studied PI3K regulatory subunit, p85α, which also binds and regulates the PIP3 phosphatasePten,and the lipogenic transcription factorXbp1.Mutations in humanPIK3R1cause SHORT syndrome, featuring lipodystrophy and severe insulin resistance which, uniquely, are uncoupled from fatty liver and dyslipidemia. We describe a novel mouse model of SHORT syndrome made by knock in of thePik3r1Y657X mutation. Homozygous embryos die at E11.5, while heterozygous mice exhibit pre-and postnatal growth impairment with diminished placental vascularity. Adipose tissue accretion on high fat feeding was reduced, however adipocyte size was unchanged and preadipocyte differentiationex vivounimpaired. Despite severe insulin resistance, heterozygous mice were hypolipidemic, and plasma adiponectin, liver weight, cholesterol, glycogen and triglyceride content were unchanged. Mild downregulation of lipogenicSrebp1, Srebp2andChrebptranscriptional activity but no suppression ofXbp1target genes was seen after fasting. These findings give new insights into the developmental role ofPik3r1,and establish a model of lipodystrophic insulin resistance dissociated from dyslipidemia as seen in SHORT syndrome.
DHSpred: support-vector-machine-based human DNase I hypersensitive sites prediction using the optimal features selected by random forest
Authors: Manavalan Balachandran , Shin Tae Hwan , Lee Gwang
Published: November 2017

DNase I hypersensitive sites (DHSs) are genomic regions that provide important information regarding the presence of transcriptional regulatory elements and the state of chromatin. Therefore, identifying DHSs in uncharacterized DNA sequences is crucial for understanding their biological functions and mechanisms. Although many experimental methods have been proposed to identify DHSs, they have proven to be expensive for genome-wide application. Therefore, it is necessary to develop computational methods for DHS prediction. In this study, we proposed a support vector machine (SVM)-based method for predicting DHSs, called DHSpred (DNase I Hypersensitive Site predictor in human DNA sequences), which was trained with 174 optimal features. The optimal combination of features was identified from a large set that included nucleotide composition and di- and trinucleotide physicochemical properties, using a random forest algorithm. DHSpred achieved a Matthews correlation coefficient and accuracy of 0.660 and 0.871, respectively, which were 3% higher than those of control SVM predictors trained with non-optimized features, indicating the efficiency of the feature selection method. Furthermore, the performance of DHSpred was superior to that of state-of-the-art predictors. An online prediction server has been developed to assist the scientific community, and is freely available at:http://www.thegleelab.org/DHSpred.html.
MEGAN-LR: New algorithms allow accurate binning and easy interactive exploration of metagenomic long reads and contigs
Authors: Huson Daniel H. , Albrecht Benjamin , Bagci Caner , Bessarab Irina , Gorska Anna , Jolic Dino , Williams Rohan B.H.
Published: November 2017

Background

There are numerous computational tools for taxonomic or functional analysis of microbiome samples, optimized to run on hundreds of millions of short, high quality sequencing reads. Programs such as MEGAN allow the user to interactively navigate these large datasets. Long read sequencing technologies continue to improve and produce increasing numbers of longer reads (of varying lengths in the range of 10k-1M bps, say), but of low quality. There is an increasing interest in using long reads in microbiome sequencing and there is a need to adapt short read tools to long read datasets.

Methods

We describe a new LCA-based algorithm for taxonomic binning, and an interval-tree based algorithm for functional binning, that are explicitly designed for long reads and assembled contigs. We provide a new interactive tool for investigating the alignment of long reads against reference sequences. For taxonomic and functional binning, we propose to use LAST to compare long reads against the NCBI-nr protein reference database so as to obtain frame-shift aware alignments, and then to process the results using our new methods.

Results

All presented methods are implemented in the open source edition of MEGAN and we refer to this new extension as MEGAN-LR (MEGAN long read). We evaluate the LAST+MEGAN-LR approach in a simulation study, and on a number of mock community datasets consisting of Nanopore reads, PacBio reads and assembled PacBio reads. We also illustrate the practical application on a Nanopore dataset that we sequenced from an anammox bio-rector community.
Altered levels ofhsromegalncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation inDrosophila
Authors: Ray Mukulika , Singh Gunjan , Lakhotia Subhash C.
Published: November 2017

We exploited the high Ras activity induced differentiation of supernumerary R7 cells inDrosophilaeyes to examine ifhsrωlncRNAs influence active Ras signaling. Surprisingly, either down- or up-regulation ofhsrωlncRNAs insev-GAL4>RasV12expressing eye discs resulted in complete pupal lethality and substantially greater increase in R7 photoreceptor number at the expense of cone cells. Enhanced nuclear p-MAPK and presence ofsev-GAL4driven RasV12bound RafRBDFLAG in cells not expressing thesev-GAL4driver indicated non-cell autonomous spread of Ras signaling whenhsrωlevels were co-altered. RNA-sequencing revealed that down-and up-regulation ofhsrωtranscripts insev-GAL4>RasV12expressing eye discs elevated transcripts of positive or negative modulators, respectively, of Ras signaling so that either condition enhances it. Alteredhsrωtranscript levels insev-GAL4>RasV12expressing discs also affected sn/sno/sca RNAs and some other RNA processing transcript levels. Post-transcriptional changes due to the disrupted intra-cellular dynamicity of omega speckle associated hnRNPs and other RNA-binding proteins that follow down- or up-regulation ofhsrωlncRNAs appear to be responsible for the further elevated Ras signaling. Cell autonomous and non-autonomous enhancement of Ras signaling by lncRNAs likehsrωhas implications for cell signaling during high Ras activity commonly associated with some cancers.

Highlights

Our findings highlight roles ofhsrωlncRNAs in conditionally modulating the important Ras signaling pathway and provide evidence for cell non-autonomous Ras signaling inDrosophilaeye discs.
Population level mitogenomics of the long-lived Greater Mouse-eared bat,Myotis myotis, reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing
Authors: Jebb David , Foley Nicole M. , Whelan Conor V. , Touzalin Frédéric , Puechmaille Sebastien J. , Teeling Emma C.
Published: November 2017

Background

Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The “Free Radical Theory of Ageing” (FTRA) posits that a high metabolic rate leads to mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest lived order of mammals despite their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age as predicted by the FRTA, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long livedMyotis myotisas they age.

Results

In total, blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria were sequenced, with a subset sampled over multiple years. The majority of heteroplasmies, 77.6%, were at a frequency below 5%. Oxidative mutations were not the primary source of heteroplasmies and present in only a small number of individuals, likely representing local oxidative stress events. There was a significant positive correlation between age and heteroplasmy, with a rate of increase of 0.13 sites per year. Longitudinal data from recaptured individuals show heteroplasmy is dynamic, and does not increase uniformly over time.

Conclusions

We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy which underscores the FRTA. Most heteroplasmies were at low frequency and are primarily transitions. Heteroplasmy increased with age, however how this contributes to ageing is unclear, as heteroplasmy was dynamic, questioning its presumed role as a primary driver of ageing.
VarExp: Estimating variance explained by Genome-Wide GxE summary statistics
Authors: Laville Vincent , Bentley Amy R. , Privé Florian , Zhu Xiafoeng , Gauderman Jim , Winkler Thomas W , Province Mike , Rao DC , Aschard Hugues ,   on behalf of the CHARGE Gene-Lifestyle Interactions Working Group
Published: November 2017

Many genomic analyses, such as genome-wide association studies (GWAS) or genome-wide screening for Gene-Environment (GxE) interactions have been performed to elucidate the underlying mechanisms of human traits and diseases. When the analyzed outcome is quantitative, the overall contribution of identified genetic variants to the outcome is often expressed as the percentage of phenotypic variance explained. In practice, this is commonly estimated using individual genotype data. However, using individual-level data faces practical and ethical challenges when the GWAS results are derived in large consortia through meta-analysis of results from multiple cohorts. In this work, we present a R package, “VarExp”, that allows for the estimation of the percentage of phenotypic variance explained by variants of interest using summary statistics only. Our package allows for a range of models to be evaluated, including marginal genetic effects, GxE interaction effects, and main genetic and interaction effects jointly. Its implementation integrates all recent methodological developments on the topic and does not need external data to be uploaded by users.

The R source code, tutorial and associated example are available at https://gitlab.pasteur.fr/statistical-genetics/VarExp.git.
Determinants of Transcription Initiation Directionality in Metazoans
Authors: Ibrahim Mahmoud M. , Karabacak Aslihan , Glahs Alexander , Kolundzic Ena , Hirsekorn Antje , Carda Alexa , Tursun Baris , Zinzen Robert P. , Lacadie Scott A. , Ohler Uwe
Published: November 2017

Divergent transcription from promoters and enhancers is pervasive in many species, but it remains unclear if it is a general and passive feature of all eukaryotic cis regulatory elements. To address this, we define promoters and enhancers in C. elegans, D. melanogaster and H. sapiens using ATAC-Seq and investigate the determinants of their transcription initiation directionalities by analyzing genome-wide nascent, cap-selected, polymerase run-on assays. All three species initiate divergent transcription from separate core promoter sequences. Sequence asymmetry downstream of forward and reverse initiation sites, known to be important for termination and stability in H. sapiens, is unique in each species. Chromatin states of divergent promoters are not entirely conserved, but in all three species, the levels of histone modifications on the +1 nucleosome are independent from those on the -1 nucleosome, arguing for independent initiation events. This is supported by an integrative model of H3K4me3 levels and core promoter sequence that is highly predictive of promoter directionality and of two types of promoters: those with balanced initiation directionality and those with skewed directionality. Lastly, D. melanogaster enhancers display variation in chromatin architecture depending on enhancer location, and D. melanogaster promoter regions with dual enhancer/promoter potential are enriched for divergent transcription. Our results point to a high degree of variation in regulatory element transcription initiation directionality within and between metazoans, and to non-passive regulatory mechanisms of transcription initiation directionality in those species.
The urinary microbiome associated with bladder cancer
Authors: Popović Viljemka Bučević , Šitum Marijan , Chow Cheryl-Emiliane T. , Chan Luisa S. , Roje Blanka , Terzić Janoš
Published: November 2017

Recent findings suggest that microorganisms inhabiting the human body can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from male patients diagnosed with primary or recurrent, non-muscle invasive bladder cancers, and from healthy, age-matched individuals were analysed using 16S Illumina MiSeq sequencing. Our result show that the most abundant phylum in both groups wasFirmicutes, followed byActinobacteria, BacteroidetesandProteobacteria. While microbial diversity and overall microbiome composition were not significantly different between bladder cancer and healthy samples, we identified specific operational taxonomic units (OTUs) that were significantly more abundant (p < 0.05) in either type of samples. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genusFusobacterium, a possible protumorigenic pathogen. Three OTUs more abundant in healthy urines were from generaVeillonella, StreptococcusandCorynebacterium. Detected microbiome changes suggest that microbiome may be a factor in bladder cancer pathology, and the clinical implications of reported results remain to be explored.
Paleocene origin of the Neotropical lineage of cleptoparasitc bees Ericrocidini-Rhathymini (Hymenoptera, Apidae)
Authors: Martins Aline C. , Luz David R. , Melo Gabriel A. R.
Published: November 2017

Cleptoparasitic bees abandoned the pollen collecting for their offspring and lay their eggs on other bees’ provisioned nests. Also known as cuckoo bees they belong to several lineages, especially diverse in Apinae. We focused on a lineage of Apinae cleptoparasitic bees, the clade Ericrocidini+Rhathymini, which attack nests of the oil-collecting bees. We sequenced five genes for a broad sampling in this clade plus a large outgroup and reconstruct phylogeny and divergence times. We confirmed the monophyly of the clade Ericrocidini+Rhathymini and its position inside the ericrocidine line, together with the tribes Protepeolini, Isepeolini and Coelioxoidini. Our results corroborate the current taxonomic classification.Ericrocisis the basal most lineage in Ericrocidini and the position ofAcanthopusand the most diverse genusMesopliawere inconclusive. Ericrocidini+Rhathymini diverged fromParepeolus aterrimus74 mya in the Cretaceous. Considering the robust molecular evidence of their sister relationships, the striking differences on the first instar larvae morphology of the two groups are probably adaptations to the distinct nesting biology of their hosts. As other parasites in the ericrocidine line, both groups possess larvae adapted to kill the immature host and to feed on floral oil provisioned by the host female. The evolution of host specialization in the line Ericrocidini+Rhathymini retroced to the Eocene when they arose synchronously with their hosts,CentrisandEpicharis.
From tree tops to the ground: reversals to terrestrial habit inGaleandraorchids (Epidendroideae: Catasetinae)
Authors: Martins Aline C. , Bochorny Thuane , Pérez-Escobar Oscar A. , Chomicki Guillaume , Monteiro Silvana H. N. , de Camargo Smidt Eric
Published: November 2017

The colonization of the epiphytic niche of tropical forest canopies played an important role in orchid’s extraordinary diversification in the Neotropics. However, reversals to the terrestrial habit occurred sparsely in species of Epidendroideae. To better understand which factors might have been involved in reversals to terrestrial habits in the predominantly epiphytic Epidendroideae, we investigateGaleandradiversification in time and space. We hypothesized that the reversal to the terrestrial habitat is linked to the origin of open vegetation habitats in South America. We generated a time-calibrated phylogeny based on a matrix of 17 out of 20 species ofGaleandraplus outgroups and seven DNA markers. We found thatGaleandraoriginated towards end of the Miocene, about 10 Ma in Amazonia (including the Guiana Shield). The terrestrial clade originated synchronously with the rise of dry vegetation biomes, suggesting that aridification during the last 5 million years dramatically impacted the diversification of epiphytic lineages in the Neotropics. Habit is correlated with floral spur lengths and geographic range size. The longer spurs and narrower ranges are found in epiphytic species: probably adapted to a specialized pollination mode, associated to the long-tongued Euglossini bees, which also prefer forested habits. The terrestrial species presents variable floral spurs and wide distribution ranges, with evidence of self-pollination, suggesting the loss of specialized pollination system and concomitant range expansion.
Sensory cortex is optimised for prediction of future input
Authors: Singer Yosef , Teramoto Yayoi , WiĲmore Ben D. B. , King Andrew J. , Schnupp Jan W. H. , Harper Nicol S.
Published: November 2017

Neurons in sensory cortex are tuned to diverse features in natural scenes. But what determines which features neurons become selective to? Here we explore the idea that neuronal selectivity is optimised to represent features in the recent past of sensory input that best predict immediate future inputs. We tested this hypothesis using simple feedforward neural networks, which were trained to predict the next few video or audio frames in clips of natural scenes. The networks developed receptive fields that closely matched those of real cortical neurons, including the oriented spatial tuning of primary visual cortex, the frequency selectivity of primary auditory cortex and, most notably, in their temporal tuning properties. Furthermore, the better a network predicted future inputs the more closely its receptive fields tended to resemble those in the brain. This suggests that sensory processing is optimised to extract those features with the most capacity to predict future input.

Impact statement

Prediction of future input explains diverse neural tuning properties in sensory cortex.
Presidential political systems and contemporary administrative reform: Israelʼs “semi-presidentialism” as a natural experiment
Authors: Rosenbloom David H. , Segal Zeev
Published: November 2017

How suitable is the New Public Management (NPM), which developed in parliamentary systems, to presidential democracies? The answer is important to reform efforts in the U.S. federal government and in several Latin American nations. According to Fred Riggs, the requirements of successful public administration in “presidentialist” and parliamentary systems differ considerably. Israelʼs experience with reform presents a natural experiment that supports Riggs” theory of presidentialisi administration. Israel embarked on NPM-style reforms when it was a pure parliamentary democracy. Its reform program was revised in ways that fit Riggsʼ prescriptions for presidentialism after the country adopted major electoral and structural changes that made it “semi-presidentialist.” Although a single case study of limited duration, the Israeli experience suggests that there is a distinctive logic to presidentialist administration that is readily understood by government officials who perforce must assess the demands of constitutional structure on administrative arrangements.
Positioning public administration curriculum to add value: the case for “transferrable skills”
Authors: Greisler David S.
Published: November 2017

Public administration (PA) as an area of academic study and intellectual pursuit has long suffered from a lack of distinctiveness. While there is benefit inside struggle, and acknowledging that the field has advanced, there is progress remaining to be made. Focusing on the development of a skill base among Public Administrators that adds value to current vocational settings and positions the practitioner to be professionally lithe (through skills that are transferable to other public settings, quasipublic settings, and private industry) is personally and professionally healthy. To this end, mastery of statistical process control, process improvement, lean service/manufacturing, six sigma, and project management will optimally position the PA practitioner to add organizational value while concomitantly maximizing vocational flexibility
Bullying in the workplace: definition, prevalence, antecedents and consequences
Authors: Matthiesen Stig Berge , Einarsen Ståle
Published: November 2017

This article examines the phenomenon and concept of bullying in the workplace. Workplace bullying is a form of interpersonal aggression that can be both flagrant and subtle, but is mainly characterized by its persistency and long term duration. The relationships between bullying and related concepts such as workplace aggression and interpersonal conflict are discussed. With reference to previous empirical research as well as theoretical contributions, an attempt is made to clarify some important aspects about the phenomenon, such as various subtypes of workplace bullying. Empirical findings on prevalence, antecedents and outcome factors are outlined and reviewed. The paper also discusses the dose-response perspective.
Effect of entrepreneurial and market orientation on consumer engagement and performance of manufacturing SMEs
Authors: Mamun Abdullah Al , Mohiuddin Muhammad , Fazal Syed Ali , Ahmad Ghazali Bin
Published: November 2017

Purpose

This study aims to examine the effect of entrepreneurial and market orientations on consumer engagement and the performance of manufacturing small- and medium-sized enterprises (SMEs) under the premise of the resource-based view (RBV) theory.

Design/methodology/approach

This study adopts a cross-sectional design, and quantitative data were collected from 360 manufacturing SMEs in Peninsular Malaysia. SMEs were selected using a stratified multi-stage sampling method from a total of 37,861 manufacturing SMEs. The respondents were selected from Selangor, Johor, Penang, Perak, Kelantan and Terengganu, as these states make up the majority (79 per cent) of the manufacturing SMEs in Malaysia.

Findings

Entrepreneurial and market orientations have statistically significant positive effects on consumer engagement. Consumer engagement in turn positively affects the performance of manufacturing SMEs in Peninsular Malaysia. Findings also revealed a partial mediation of consumer engagement between entrepreneurial and market orientations on performance.

Research limitations/implications

A larger sample size may improve the generalizability of the findings. Managers may be able to apply the findings of this paper in developing strategies for their manufacturing SMEs, specifically, by focusing on entrepreneurial and market orientation to raise consumer engagement and to improve the overall performances of their SMEs.

Originality/value

This study focuses on manufacturing SMEs in Malaysia, an emerging country with conditions unique to other industrialized countries. This study aims to demonstrate that integrated entrepreneurial and market orientations have significant effects on SMEs’ performance. This relationship could be mediated by consumer engagement. Specifically, consumer orientation may influence the effect of entrepreneurial and market orientations on overall firm performance..
Aging mechanisms and intervention targets
Authors: Liu Jun‐Ping
Published: November 2017

Premature aging occurs frequently to various tissues and organs resulting in the tissue‐specific chronic diseases. The mechanisms of tissue‐specific premature aging are largely unknown. In response to environmental cues, aging may originate from cytoplasm or the nucleus of a cell with cytoplasm aging in association with organelle degeneration in terminally differentiated cells and nuclear aging with dysfunctional telomeres and irreversible cell cycle arrest in stem and cancer cells. Either cytoplasm aging or nuclear aging may cause extracellular senescence‐associated low‐grade inflammation to spread aging. Referring to the recent findings in this special issue of Healthy Aging in CEPP and beyond, we describe the molecular and cellular mechanisms of physiological aging and tissue‐specific pathological aging in chronic diseases.
China's changing diet and its impacts on greenhouse gas emissions: an index decomposition analysis
Authors: Hawkins Jacob , Ma Chunbo , Schilizzi Steven , Zhang Fan
Published: November 2017

With increasing awareness of agriculture's contribution to global greenhouse gases (GHGs) and China's position as the world's top GHG emitter, there is heightened attention to the embodied emissions in China's food consumption. China's diet has shifted to include more fruit, vegetables, meat and dairy. Not surprisingly, GHG emissions from food consumption have also increased substantially. This analysis links China's food consumption with the emissions of food production industries in China and its trade partners to determine the effects of dietary change on GHGs since 1989. We utilise high‐resolution food production and emissions data to perform a logarithmic mean Divisia index decomposition to attribute changes in GHG emissions to the scale, supply structure, demand structure and efficiency effects resulting from Chinese dietary changes over a 20‐year period. This study finds that while countries supplying food to China contribute little to China's food‐related GHGs, demands for meat and dairy play a much larger role, driving up emissions. The overall scale of increased consumption of all food further propels growth in GHG emissions. Results indicate, however, that while food consumption in China more than doubles between 1989 and 2009 improvements in technological efficiency limit the rate of increase.
Active Packaging Applications for Food
Authors: Yildirim Selçuk , Röcker Bettina , Pettersen Marit Kvalvåg , Nilsen‐Nygaard Julie , Ayhan Zehra , Rutkaite Ramune , Radusin Tanja , Suminska Patrycja , Marcos Begonya , Coma Véronique
Published: November 2017

The traditional role of food packaging is continuing to evolve in response to changing market needs. Current drivers such as consumer's demand for safer, “healthier,” and higher‐quality foods, ideally with a long shelf‐life; the demand for convenient and transparent packaging, and the preference for more sustainable packaging materials, have led to the development of new packaging technologies, such as active packaging (AP). As defined in the European regulation (EC) No 450/2009, AP systems are designed to “deliberately incorporate components that would release or absorb substances into or from the packaged food or the environment surrounding the food.” Active packaging materials are thereby “intended to extend the shelf‐life or to maintain or improve the condition of packaged food.” Although extensive research on AP technologies is being undertaken, many of these technologies have not yet been implemented successfully in commercial food packaging systems. Broad communication of their benefits in food product applications will facilitate the successful development and market introduction. In this review, an overview of AP technologies, such as antimicrobial, antioxidant or carbon dioxide‐releasing systems, and systems absorbing oxygen, moisture or ethylene, is provided, and, in particular, scientific publications illustrating the benefits of such technologies for specific food products are reviewed. Furthermore, the challenges in applying such AP technologies to food systems and the anticipated direction of future developments are discussed. This review will provide food and packaging scientists with a thorough understanding of the benefits of AP technologies when applied to specific foods and hence can assist in accelerating commercial adoption.
Prospects on the evolutionary mitogenomics of plants: A case study on the olive family (Oleaceae)
Authors: Van de Paer Céline , Bouchez Olivier , Besnard Guillaume
Published: November 2017

The mitogenome is rarely used to reconstruct the evolutionary history of plants, contrary to nuclear and plastid markers. Here, we evaluate the usefulness of mitochondrial DNA for molecular evolutionary studies in Oleaceae, in which cases of cytoplasmic male sterility (CMS) and of potentially contrasted organelle inheritance are known. We compare the diversity and the evolution of mitochondrial and chloroplast genomes by focusing on the olive complex and related genera. Using high‐throughput techniques, we reconstructed complete mitogenomes (ca. 0.7 Mb) and plastomes (ca. 156 kb) for six olive accessions and one Chionanthus. A highly variable organization of mitogenomes was observed at the species level. In olive, two specific chimeric genes were identified in the mitogenome of lineage E3 and may be involved in CMS. Plastid‐derived regions (mtpt) were observed in all reconstructed mitogenomes. Through phylogenetic reconstruction, we demonstrate that multiple integrations of mtpt regions have occurred in Oleaceae, but mtpt regions shared by all members of the olive complex derive from a common ancestor. We then assembled 52 conserved mitochondrial gene regions and complete plastomes of ten additional accessions belonging to tribes Oleeae, Fontanesieae and Forsythieae. Phylogenetic congruence between topologies based on mitochondrial regions and plastomes suggests a strong disequilibrium linkage between both organellar genomes. Finally, while phylogenetic reconstruction based on plastomes fails to resolve the evolutionary history of maternal olive lineages in the Mediterranean area, their phylogenetic relationships were successfully resolved with complete mitogenomes. Overall, our study demonstrates the great potential of using mitochondrial DNA in plant phylogeographic and metagenomic studies.
Discussion of “Financial Statement Comparability and the Efficiency of Acquisition Decisions”
Authors: Klein April
Published: November 2017

Chen, Collins, Kravet, and Mergenthaler (CCKM, ) is an empirical investigation of whether, after controlling for other known determinants of an acquirer's abnormal stock returns and expected and realized synergies, financial statement comparability impacts the investment decisions surrounding the acquirer's purchase of another company. The primary result is that higher financial statement comparability, as measured by De Franco, Kothari, and Verdi (DKV, ), yields improvements on outcomes associated with mergers and acquisitions. This discussion presents some criticisms of the DKV measure as applied to this study; the main criticism being whether the DKV measure captures accounting comparability or the risk of the target firm. The empirical results presented in CCKM are consistent with both explanations, thus making it difficult to disentangle CCKM's interpretation from an alternative explanation of their empirical findings.
MicroRNA‐21 Contributes to Reduced Microvascular Function in Binge Drinking Young Adults
Authors: Bian Jing‐Tan , Piano Mariann R. , Kotlo Kumar U. , Mahmoud Abeer M. , Phillips Shane A.
Published: November 2017

Background

Binge drinking is associated with increased risk for cardiovascular (CV) disease. MicroRNA‐21 (miR21) is up‐regulated in the setting of excessive alcohol consumption and CV disease. Therefore, the goal of this study was to examine the vasodilatory responses to flow and acetylcholine (ACh) in the absence and presence of an anti‐miR21 inhibitor in the microcirculation of young adult repeated binge drinkers (BDs).

Methods

Gluteal subcutaneous adipose tissue biopsies were obtained from young adults (18 to 30 years, n = 35 vessels from BDs and n = 28 vessels from abstainers). Resistance arteries (RAs) were isolated, incubated with anti‐miR21 or a negative control (NC) to miR21 (12 hours; 50 nM), and lumen diameters measured with video microscopy. miR21 of adipose tissues was determined by quantitative polymerase chain reaction.

Results

Flow‐induced dilation and ACh‐induced dilation (AChID) were reduced in BDs as compared to abstainers. The miR21 inhibitor but not the NC abrogated these effects in BDs, but did not affect vasodilation in abstainers. Nitric oxide synthase inhibition with L‐NAME reduced vasodilation in abstainers but not in BDs. In BDs, vasodilation was reduced by L‐NAME in the presence of anti‐miR21 but not the NC. Scavenging the reactive oxygen species, hydrogen peroxide with polyethylene glycol catalase reduced dilation in BDs but did not affect the restored dilation by the miR21 inhibitor. Maximum dilation to papaverine (endothelium independent) was similar between groups and unaffected by pharmacological inhibition. Finally, vascular endogenous miR21 was increased in BDs compared to abstainers.

Conclusions

Endogenous miR21 is increased in RAs of young BDs, leading to reduced flow and AChID in the microcirculation.
Communities mobilizing for change on alcohol (CMCA): secondary analyses of a randomized controlled trial showing effects of community organizing on alcohol acquisition by youth in the Cherokee nation
Authors: Wagenaar Alexander C. , Livingston Melvin D. , Pettigrew Dallas W. , Kominsky Terrence K. , Komro Kelli A.
Published: November 2017

Aims

We evaluated the effects of a community organizing intervention, Communities Mobilizing for Change on Alcohol (CMCA), on the propensity of retail alcohol outlets to sell alcohol to young buyers without age identification and on alcohol acquisition behaviors of underage youth.

Design

Random assignment of community to treatment (n = 3) or control (n = 2). Student surveys were conducted four times per year for 3 years; the cohort was in 9th and 10th grades in the 2012–13 academic year. Alcohol purchase attempts were conducted every 4 weeks at alcohol retailers in each community (31 repeated waves).

Setting

The Cherokee Nation, located in northeastern Oklahoma, USA.

Participants

A total of 1399 high school students (50% male; 45% American Indian) and 113 stores licensed to sell alcohol across five study communities.

Intervention

Local community organizers formed independent citizen action teams to advance policies, procedures and practices of local institutions in ways to reduce youth access to alcohol and foster community norms opposed to teen drinking.

Measurements

Perceptions regarding police enforcement and perceived difficulty of and self‐reported actual acquisition of alcohol from parents, adults, peers and stores.

Findings

Alcohol purchases by young‐appearing buyers declined significantly, an 18 [95% confidence interval (CI) = 3, 33] percentage‐point reduction over the intervention period. Student survey results show statistically significant differences in the trajectory of perceived police enforcement, increasing 7 (4, 10) percentage points, alcohol acquisition from parents, decreasing 4 (0.1, 8) percentage points, acquisition from 21+ adults, decreasing 6 (0.04, 11) percentage points, from < 21 peers decreasing 8 (3, 13) percentage points and acquisition from stores decreasing 5 (1, 9) percentage points.

Conclusions

A community organizing intervention, Communities Mobilizing for Change on Alcohol (CMCA), is effective in reducing the availability of alcohol to underage youth in the United states. Furthermore, results indicate that the previously reported significant effects of CMCA on teen drinking operate, at least in part, through effects on alcohol access.
Obese children aged 4–6 displayed decreased fasting and postprandial ghrelin levels in response to a test meal
Authors: Önnerfält Jenny , Erlanson‐Albertsson Charlotte , Montelius Caroline , Thorngren‐Jerneck Kristina
Published: November 2017

Aim

Ghrelin is a hunger hormone that plays a role in glucose homoeostasis and its levels increase before a meal and decrease during and after eating. This study compared the fasting ghrelin and insulin levels of obese children aged 4–6 with those of normal weight children and tested postprandial ghrelin levels in the obese children after a standard breakfast.

Methods

We recruited 67 children at Lund University Hospital from 2008 to 2011. They comprised 30 obese children from a weight study and 37 normal weight children receiving minor elective surgery. Their mean ages were 4.7 ± 0.6 and 4.3 ± 0.8 years, respectively. The obese children ate a standard breakfast, and postprandial ghrelin was measured after 60 minutes.

Results

The obese children had lower ghrelin levels than the controls (p < 0.01). A significant inverse relation was found between body mass index and fasting ghrelin levels. Obese children had significantly lower fasting ghrelin levels after a standard breakfast (p < 0.01), but there were no gender‐related differences.

Conclusion

Obese children aged 4–6 years had reduced ghrelin and increased insulin levels in the fasting state and postprandial ghrelin was suppressed, suggesting that their energy metabolism was already dysregulated at this young age. Early obesity interventions are essential.
Effects of female sex hormones on folic acid–induced anti‐angiogenesis
Authors: Lee W.‐S. , Lu Y.‐C. , Kuo C.‐T. , Chen C.‐T. , Tang P.‐H.
Published: November 2017

Aim

Pregnant women have been recommended to take FA daily to prevent birth defects in the brain and spinal cord. We previously showed that folic acid (FA) exerts an anti‐angiogenic activity. As angiogenesis is important for endometrial reorganization and embryonic development, there should be some mechanisms to allow the pregnant mother and the foetus to escape from the FA‐induced anti‐angiogenesis. This study was designed to investigate the effect of female sex hormones on the FA‐induced anti‐angiogenic activity.

Methods

The protein levels and protein‐protein interaction were examined by Western blot analysis and immunoprecipitation assay respectively. The cell proliferation and migration were examined by MTT assay and wound healing assay respectively. The in vivo angiogenesis was evaluated by Matrigel angiogenesis assay.

Results

In human umbilical venous endothelial cells (HUVEC), FA receptor (FR) formed a complex with progesterone receptor (PR), oestradiol receptor (ER) and cSrc. Pregnancy levels of progesterone (P4) or oestradiol (E2) prevented FA‐induced inhibitions of proliferation and migration in HUVEC. Both E2 and P4 prevented the FA‐induced anti‐angiogenesis in vivo. Moreover, cotreatment with FA and P4 or E2 inhibited the signalling pathways involved in FA‐induced inhibitions of proliferation and migration in HUVEC.

Conclusion

Female sex hormones interrupt the FA‐induced anti‐angiogenic action through receptor‐receptor interaction.
Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies
Authors: Vinjamur Divya S. , Bauer Daniel E. , Orkin Stuart H.
Published: November 2017

The major β‐haemoglobinopathies, sickle cell disease and β‐thalassaemia, represent the most common monogenic disorders worldwide and a steadily increasing global disease burden. Allogeneic haematopoietic stem cell transplantation, the only curative therapy, is only applied to a small minority of patients. Common clinical management strategies act mainly downstream of the root causes of disease. The observation that elevated fetal haemoglobin expression ameliorates these disorders has motivated longstanding investigations into the mechanisms of haemoglobin switching. Landmark studies over the last decade have led to the identification of two potent transcriptional repressors of γ‐globin, BCL11A and ZBTB7A. These regulators act with additional trans‐acting epigenetic repressive complexes, lineage‐defining factors and developmental programs to silence fetal haemoglobin by working on cis‐acting sequences at the globin gene loci. Rapidly advancing genetic technology is enabling researchers to probe deeply the interplay between the molecular players required for γ‐globin (HBG1/HBG2) silencing. Gene therapies may enable permanent cures with autologous modified haematopoietic stem cells that generate persistent fetal haemoglobin expression. Ultimately rational small molecule pharmacotherapies to reactivate HbF could extend benefits widely to patients.