bluuebunny/crossref_metadata_2025 huggingface dataset:
Farm-to-fork investigation of an outbreak of Shiga toxin-producing Escherichia coli O157
Authors: Wilson Deborah , Dolan Gayle , Aird Heather , Sorrell Shirley , Dallman Timothy J. , Jenkins Claire , Robertson Lucy , Gorton Russell
Published: February 2018

Fifteen cases of Shiga toxin-producing Escherichia coli (STEC) O157 infection were associated with the consumption of contaminated food from two related butchers’ premises in the north-east of England. Ten cases were admitted to hospital and seven cases developed haemolytic uraemic syndrome. A case control study found a statistically significant association with the purchase of raw and/or ready-to-eat (RTE) food supplied by the implicated butchers’ shops. Isolates of STEC O157 were detected in two raw lamb burgers taken from one of the butchers’ premises. Subsequent environmental sampling identified STEC O157 in bovine faecal samples on the farm supplying cattle to the implicated butchers for slaughter. Whole genome sequencing (WGS) was performed on the Illumina HiSeq 2500 platform on all cultures isolated from humans, food and cattle during the investigation. Quality trimmed Illumina reads were mapped to the STEC O157 reference genome Sakai using bwa-mem, and single nucleotide polymorphisms (SNPs) were identified using gatk2. Analysis of the core genome SNP positions (>90 % consensus, minimum depth 10×, mapping quality (MQ)≥30) revealed that all isolates from humans, food and cattle differed by two SNPs. WGS analysis provided forensic-level microbiological evidence to support the epidemiological links between the farm, the butchers’ premises and the clinical cases. Cross-contamination from raw meat to RTE foods at the butchers’ premises was the most plausible transmission route. The evidence presented here highlights the importance of taking measures to mitigate the risks of cross-contamination in this setting.
Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae
Authors: Basgall Erianna M. , Goetting Samantha C. , Goeckel Megan E. , Giersch Rachael M. , Roggenkamp Emily , Schrock Madison N. , Halloran Megan , Finnigan Gregory C.
Published: February 2018

Given the widespread use and application of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas gene editing system across many fields, a major focus has been the development, engineering and discovery of molecular means to precisely control and regulate the enzymatic function of the Cas9 nuclease. To date, a variety of Cas9 variants and fusion assemblies have been proposed to provide temporally inducible and spatially controlled editing functions. The discovery of a new class of ‘anti-CRISPR’ proteins, evolved from bacteriophage in response to the prokaryotic nuclease-based immune system, provides a new platform for control over genomic editing. One Cas9-based application of interest to the field of population control is that of the ‘gene drive’. Here, we demonstrate use of the AcrIIA2 and AcrIIA4 proteins to inhibit active gene drive systems in budding yeast. Furthermore, an unbiased mutational scan reveals that titration of Cas9 inhibition may be possible by modification of the anti-CRISPR primary sequence.
Most calbindin-immunoreactive neurons, but few calretinin-immunoreative neurons, express the m1 acetylcholine receptor in the middle temporal visual area of the macaque monkey
Authors: Coppola Jennifer J. , Disney Anita A.
Published: February 2018

Release of the neuromodulator acetylcholine into cortical circuits supports cognition, although its precise role and mechanisms of action are not well-understood. Little is known about functional differences in cholinergic modulatory effects across cortical model systems, but anatomical evidence suggests that such differences likely exist because, for example, the expression of cholinergic receptors differs profoundly both within and between species. In the primary visual cortex (V1) of macaque monkeys, cholinergic receptors are strongly expressed by inhibitory interneurons. Here, we examine m1 muscarinic acetylcholine receptor expression by two subclasses of inhibitory interneurons—identified by their expression of the calcium-binding proteins calbindin and calretinin—in the middle temporal extrastriate area (MT) of the macaque. Using dual-immunofluorescence confocal microscopy, we find that the majority of calbindin-immunoreative neurons (55%) and only few calretinin-immunoreactive neurons (10%) express the m1 acetylcholine receptor. This differs from the pattern observed in V1 of the same species, lending further support to the notion that cholinergic modulation in cortex is tuned such that different cortical compartments will respond to acetylcholine release in different ways.
p53deletion rescues lethal microcephaly in a mouse model with neural stem cell abscission defects
Authors: Little Jessica Neville , Dwyer Noelle D.
Published: February 2018

Building a cerebral cortex of the proper size involves balancing rates and timing of neural stem cell (NSC) proliferation, neurogenesis, and cell death. The cellular mechanisms connecting genetic mutations to brain malformation phenotypes are still poorly understood. Microcephaly may result when NSC divisions are too slow, produce neurons too early, or undergo apoptosis, but the relative contributions of these cellular mechanisms to various types of microcephaly are not understood. We previously showed that mouse mutants inKif20b(formerly calledMphosph1, Mpp1, orKRMP1) have small cortices that show elevated apoptosis, and defects in maturation of NSC midbodies, which mediate cytokinetic abscission. Here we test the contribution of intrinsic NSC apoptosis to brain size reduction in this lethal microcephaly model. By making double mutants with the pro-apoptotic genesBaxandTrp53 (p53), we find that apoptosis of cortical NSCs accounts for most of the microcephaly, but that there is a significant apoptosis-independent contribution as well. Remarkably, heterozygousp53deletion is sufficient to fully rescue survival of theKif20bmutant into adulthood. In addition, the NSC midbody maturation defects are not rescued byp53deletion, showing that they are either upstream of p53 activation, or in a parallel pathway. Thus, this work potentially identifies a novel midbody-mediated pathway for p53 activation, and elucidates both NSC apoptosis and abscission mechanisms that could underlie human microcephaly or other brain malformations.
The thalamus regulates retinoic acid signaling and development of parvalbumin interneurons in postnatal mouse prefrontal cortex
Authors: Larsen Rachel , Proue Alatheia , Scott Earl Parker , Christiansen Matthew , Nakagawa Yasushi
Published: February 2018

Abnormal development of GABAergic interneurons in the prefrontal cortex (PFC) is implicated in a number of psychiatric disorders. Yet, developmental mechanisms for these neurons are poorly understood. Here we show that the retinoic acid-degrading enzyme CYP26B1 is temporally expressed specifically in postnatal frontal cortex in mice, and its genetic deletion results in an increased density of parvalbumin (PV)-expressing interneurons in medial PFC during postnatal development. Furthermore, initiation ofCyp26b1expression in neonatal PFC depends on the connections between the thalamus and the neocortex. Thus, the thalamus has a postnatal role in regulating PV neuron development in PFC by inducingCyp26b1and thereby restricting retinoic acid signaling. Prenatally, the lack of thalamic input causes an aberrant radial distribution of medial ganglionic eminence-derived interneurons throughout the cortex. Therefore, the thalamus controls PV neuron development in PFC both by region-specific and cortex-wide mechanisms.
Macropinocytosis overcomes directional bias due to hydraulic resistance to enhance space exploration by dendritic cells
Authors: Moreau Hélène D. , Blanch-Mercader Carles , Attia Rafaele , Alraies Zahraa , Maurin Mathieu , Bousso Philippe , Joanny Jean-François , Voituriez Raphaël , Piel Matthieu , Lennon-Duménil Ana-Maria
Published: February 2018

The migration of immune cells is guided by specific chemical signals, such as chemokine gradients. Their trajectories can also be diverted by physical cues and obstacles imposed by the cellular environment, such as topography, rigidity, adhesion, or hydraulic resistance. On the example of hydraulic resistance, it was shown that neutrophil preferentially follow paths of least resistance, a phenomenon referred to as barotaxis. We here combined quantitative imaging and physical modeling to show that barotaxis results from a force imbalance at the scale of the cell, which is amplified by the acto-myosin intrinsic polarization capacity. Strikingly, we found that macropinocytosis specifically confers to immature dendritic cells a unique capacity to overcome this physical bias by facilitating external fluid transport across the cell, thereby enhancing their space exploration capacity in vivo and promoting their tissue-patrolling function. Conversely, mature dendritic cells, which down-regulate macropinocytosis, were found to be sensitive to hydraulic resistance. Theoretical modeling suggested that barotaxis, which helps them avoid dead-ends, may accelerate their migration to lymph nodes, where they initiate adaptive immune responses. We conclude that the physical properties of the microenvironment of moving cells can introduce biases in their migratory behaviors but that specific active mechanisms such as macropinocytosis have emerged to diminish the influence of these biases, allowing motile cells to reach their final destination and efficiently fulfill their functions.
In vivo CRISPR-Cas gene editing with no detectable genome-wide off-target mutations
Authors: Akcakaya Pinar , Bobbin Maggie L. , Guo Jimmy A. , Lopez Jose M. , Clement M. Kendell , Garcia Sara P. , Fellows Mick D. , Porritt Michelle J. , Firth Mike A. , Carreras Alba , Baccega Tania , Seeliger Frank , Bjursell Mikael , Tsai Shengdar Q. , Nguyen Nhu T. , Nitsch Roberto , Mayr Lorenz M. , Pinello Luca , Bohlooly-Y Mohammad , Aryee Martin J. , Maresca Marcello , Joung J. Keith
Published: February 2018

CRISPR-Cas genome-editing nucleases hold substantial promise for human therapeutics1–5 but identifying unwanted off-target mutations remains an important requirement for clinical translation6, 7. For ex vivo therapeutic applications, previously published cell-based genome-wide methods provide potentially useful strategies to identify and quantify these off-target mutation sites8–12. However, a well-validated method that can reliably identify off-targets in vivo has not been described to date, leaving the question of whether and how frequently these types of mutations occur. Here we describe Verification of In Vivo Off-targets (VIVO), a highly sensitive, unbiased, and generalizable strategy that we show can robustly identify genome-wide CRISPR-Cas nuclease off-target effects in vivo. To our knowledge, these studies provide the first demonstration that CRISPR-Cas nucleases can induce substantial off-target mutations in vivo, a result we obtained using a deliberately promiscuous guide RNA (gRNA). More importantly, we used VIVO to show that appropriately designed gRNAs can direct efficient in vivo editing without inducing detectable off-target mutations. Our findings provide strong support for and should encourage further development of in vivo genome editing therapeutic strategies.
NF1deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer
Authors: Dischinger Patrick S. , Tovar Elizabeth A. , Essenburg Curt J. , Madaj Zachary B. , Gardner Eve , Callaghan Megan , Turner Ashley N. , Challa Anil K. , Kempston Tristan , Eagleson Bryn , Kesterson Robert A. , Bronson Roderick T. , Bowman Megan J. , Graveel Carrie R. , Steensma Matthew R.
Published: February 2018

The key negative regulatory gene of the RAS pathway,NF1, is mutated or deleted in numerous cancer types and is associated with increased cancer risk and drug resistance. Even though women with neurofibromatosis (germlineNF1mutations) have a substantially increased breast cancer risk at a young age andNF1is commonly mutated in sporadic breast cancers, we have a limited understanding of the role ofNF1in breast cancer. Much of our understanding of the mechanisms underlying the functional loss ofNF1comes from mouse models that do not completely recapitulate the phenotypes of humanNF1. We utilized CRISPR-Cas9 gene editing to createNf1rat models to evaluate the effect ofNf1deficiency on tumorigenesis. The resultingNf1indels induced highly penetrant, aggressive mammary adenocarcinomas that express estrogen receptor and progesterone receptor. We identified distinctNf1isoforms that were altered during tumorigenesis.

To evaluateNF1in human breast cancer, we analyzed genomic changes in a breast cancer dataset of 2,000 clinically annotated breast cancers. We foundNF1shallow deletions in 25% of sporadic breast cancers, which correlated with poor clinical outcome. To identify biological networks impacted byNF1deficiency, we constructed gene co-expression networks using weighted gene correlation network analysis (WGCNA) and identified a network connected toESR1(estrogen receptor). Moreover,NF1-deficient cancers correlated with established RAS activation signatures. Estrogen-dependence was verified by estrogen-ablation inNf1rats where rapid tumor regression was observed. These results demonstrated the significant role NF1 plays in both NF1-related breast cancer and sporadic breast cancer.
Prediction of Optimal Growth Temperature using only Genome Derived Features
Authors: Sauer David B. , Wang Da-Neng
Published: February 2018

Optimal growth temperature is a fundamental characteristic of all living organisms. Knowledge of this temperature is central to the study the organism, the thermal stability and temperature dependent activity of its genes, and the bioprospecting of its genome for thermally adapted proteins. While high throughput sequencing methods have dramatically increased the availability of genomic information, the growth temperatures of the source organisms are often unknown. This limits the study and technological application of these species and their genomes. Here, we present a novel method for the prediction of growth temperatures of prokaryotes using only genomic sequences. By applying the reverse ecology principle that an organism’s genome includes identifiable adaptations to its native environment, we can predict a species’ optimal growth temperature with an accuracy of 4.69 °C root-mean-square error and a correlation coefficient of 0.908. The accuracy can be further improved for specific taxonomic clades or by excluding psychrophiles. This method provides a valuable tool for the rapid calculation of organism growth temperature when only the genome sequence is known.
Elaboration, structural study and validation of a new NASICON-type structure, Na0.72(Cr0.48,Al1.52)(Mo2.77,Al0.23)O12
Authors: Sonni Manel , Jendoubi Imen , Zid Mohamed Faouzi
Published: February 2018

The title compound, sodium chromium/aluminium molybdenum/aluminium dodecaoxide, Na0.72Cr0.48Al1.74Mo2.77O12, was prepared by solid-state reaction. Its crystal structure is related to NaSICON-type compounds. The framework is built up fromM1O6(M1 = Cr/Al) octahedra andM2O4(M2 = Mo/Al) tetrahedra interconnected by corners. The three-dimensional framework contains cavities in which sodium cations are located. Two validation models (BVS and CHARDI) were used to confirm the proposed structural model. The mobility of Na+ions in the structure has been investigated by theoretical means.
Risk and protective factors for the course of post-traumatic stress disorder in frontline workers after the Christchurch, New Zealand earthquake
Authors: McBride David , Porter Nancy , Lovelock Kirsten , Shepherd Daniel , Zubizaretta Maria , Burch James
Published: February 2018

Purpose

The purpose of this paper is to describe risk and protective factors for symptoms of post-traumatic stress disorder (PTSD) experienced over a 1.5-year period among both frontline and “non-traditional” responders to the 2010 and 2011 earthquakes in Christchurch, New Zealand.

Design/methodology/approach

A longitudinal survey administered to Christchurch workers with referents from the city of Hamilton at 6, 12 and 18 months after the 2011 earthquake. Potential risk and protective determinants were assessed by questionnaire items at baseline and over time, the outcome being PTSD as assessed by the PTSD Checklist-Civilian version. A longitudinal latent class analysis identified groups with similar trajectories of PTSD.

Findings

A total of 226 individuals, 140 (26 per cent) from Christchurch and 86 (16 per cent) from Hamilton, participated at baseline, 180 at 12 and 123 at 18 months, non-traditional responders forming the largest single group. Two latent classes emerged, with PTSD (21 per cent) and without PTSD (79 per cent), with little change over the 18-month period. Class membership was predicted by high scores in the Social Support and Impact of Events scale items, Health-related Quality of Life scores being protective. PTSD scores indicative of distress were found in females, and predicted by burnout risk, behavioural disengagement and venting.

Practical implications

Non-traditional responders should be screened for PTSD. Social support should be considered with the promotion of adaptive coping mechanisms.

Originality/value

The strength was longitudinal follow-up over an 18-month period, with demonstration of how the potential determinants influenced the course of PTSD over time.
Does “meaningful gamification” address gen Y needs? Exploring its influence on creating meaningful engagement for gen Y workers
Authors: Bhattacharyya Pratishtha , Jena Lalatendu Kesari , Pradhan Sajeet
Published: February 2018

Purpose

This paper aims to review the role of “meaningful gamification” in creating meaningful experience to engage Gen Y workers.

Design/methodology/approach

This paper adopts a critical, practitioner perspective to review the role of “meaningful gamification” in creating meaningful experience to engage Gen Y workers.

Findings

The author argues that “meaningful gamification” holds the potential to address Gen Y needs. In that way, it creates a base of personal relevance for the Gen Ys to relate with their own work. This ultimately translates into a meaningful experience for the employees to cherish their work.

Originality/value

The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Strategic knowledge management and enterprise social media
Authors: Archer-Brown Chris , Kietzmann Jan
Published: February 2018

Purpose

This paper aims to examine if (and how), enterprise social media (ESM) can be understood as a strategic knowledge management phenomenon to improve organizational performance.

Design/methodology/approach

This paper uses intellectual capital theory and its functional building blocks to organize different types of the ESM platforms, based on secondary data. It then connects these findings to the underling intellectual capital tenets to introduce a conceptual model that explicates how ESM impacts strategic knowledge management, and vice versa.

Findings

This paper concludes that ESM provides a unique complement to traditional strategic knowledge management. The authors argue that ESM differs substantially from other contexts in which intellectual capital has been applied, and extend intellectual capital with three appropriate dimensions (human, social and structural capital). Given the potentially disruptive nature of ESM, this framework helps firms understand the nature of the changes that are needed.

Originality/value

The paper provides the first review of the business needs that are served by the software functions and management processes under the ESM banner. This original contribution takes the intellectual capital and strategic knowledge management discussions from their usual high levels of abstraction and relates them to the real world of ESM, focusing on outcomes. Its unique “Intellectual Capital Framework for the Socially Oriented Enterprise” includes distinct, testable propositions that provide a practical approach to strategically planning, implementing and optimizing ESM.
Plant endophytes and arbuscular mycorrhizal fungi alter plant competition
Authors: Zhou Yong , Li Xia , Gao Yuan , Liu Hui , Gao Yu‐Bao , van der Heijden Marcel G. A. , Ren An‐Zhi
Published: February 2018

In nature, grasses simultaneously establish multiple symbiotic associations with endophytic fungi and arbuscular mycorrhizal fungi (AMF). The effect of these multiple interactions on competitive interactions between plants remains poorly understood.

In this study, we tested whether endophytes andAMF(Glomus mosseaeorGlomus etunicatum) alter plant competition between a subordinate plant species that associates with both symbionts (Achnatherum sibiricum) and a dominant plant species,Stipa grandis, that only associates with one symbiont (AMF). And we hypothesized that endophytes can facilitate the coexistence of the subordinate plant species (A. sibiricum) and the dominant plant species (S. grandis).

The results demonstrated that endophyte infection significantly enhanced the competitive ability of the subordinate plant species compared to the dominant plant species. The effects ofAMFon plant competition were variable and depended on the identity of theAMFspecies.Glomus etunicatumgaveA. sibiricumplants a higher competitive ability, whileG. mosseaegaveS. grandisa higher competitive ability. Simultaneous infections of both endophytes andAMFinA. sibiricumalso altered the competitive relationships withS. grandis.

In conclusion, these results suggest that endophytic fungi can facilitate the coexistence of a subordinate plant species with a dominant plant species. Moreover, endophytes could not only affect the competitive ability of the host plant directly but also indirectly by interacting with differentAMFto change the growth of competing plant species.

Aplain language summaryis available for this article.
Structural controls on photosynthetic capacity through juvenile‐to‐adult transition and needle ageing in Mediterranean pines
Authors: Kuusk Vivian , Niinemets Ülo , Valladares Fernando
Published: February 2018

Needle photosynthetic potentials strongly vary among primary (juvenile) and secondary (adult) needles (heteroblasty) inPinusspecies, but there is limited understanding of the underlying structural, diffusional and chemical controls.

We studied differences in needle photosynthetic characteristics among current‐year juvenile and adult needles and among different‐aged adult needles in Mediterranean pinesPinus halepensisMill.,P. pineaL. andP. nigraJ. F. Arnold subsp.salzmannii(Dunal) Franco, hypothesizing that needle anatomical modifications upon juvenile‐to‐adult transition lead to reduced photosynthetic capacity due to greater limitation of photosynthesis by mesophyll conductance and due to an increase in the share of support tissues at the expense of photosynthetic tissues. We also hypothesized that such alterations occur with needle ageing, but to a lower degree.

Photosynthetic capacity per dry mass was 2.4‐ to 2.7‐fold higher in juvenile needles, and this was associated with 3.4‐ to 3.7‐fold greater mesophyll diffusion conductance, 2‐ to 2.5‐fold greater maximum carboxylase activity of Rubisco (Vcmax) and 2.2‐ to 3‐fold greater capacity for photosynthetic electron transport (Jmax). The latter differences were driven by modifications in mesophyll volume fraction and changes in the share of nitrogen between structural and photosynthetic functions. Analogous changes in photosynthetic characteristics occurred with needle ageing, but their extent was less.

These results indicate that conifer foliage photosynthetic machinery undergoes a profound change from a fast return strategy in juveniles to slow return stress‐resistant strategy in adults and that this strategy shift is driven by modifications in foliage biomass investments in support and photosynthetic functions as well as by varying mesophyll diffusional controls on photosynthesis. Changes in needle morphophysiotype during tree and needle ageing need consideration in predicting changes in tree photosynthetic potentials through tree ontogeny and during and among growing seasons.

Aplain language summaryis available for this article.
Patterns of phenotypic plasticity and local adaptation in the wide elevation range of the alpine plant Arabis alpina
Authors: de Villemereuil Pierre , Mouterde Médéric , Gaggiotti Oscar E. , Till‐Bottraud Irène
Published: February 2018

Local adaptation and phenotypic plasticity are two important characteristics of alpine plants to overcome the threats caused by global changes. Among alpine species, Arabis alpina is characterised by an unusually wide altitudinal amplitude, ranging from 800 to 3,100 m of elevation in the French Alps. Two non‐exclusive hypotheses can explain the presence of A. alpina across this broad ecological gradient: adaptive phenotypic plasticity or local adaptation, making this species especially useful to better understand these phenomena in alpine plant species.

We carried out common garden experiments at two different elevations with maternal progenies from six sites that differed in altitude. We showed that (1) key phenotypic traits (morphotype, total fruit length, growth, height) display significant signs of local adaptation, (2) most traits studied are characterised by a high phenotypic plasticity between the two experimental gardens and (3) the two populations from the highest elevations lacked morphological plasticity compared to the other populations.

By combining two genome scan approaches (detection of selection and association methods), we isolated a candidate gene (Sucrose‐Phosphate Synthase 1). This gene was associated with height and local average temperature in our studied populations, consistent with previous studies on this gene in Arabidopsis thaliana.

Synthesis. Given the nature of the traits involved in the detected pattern of local adaptation and the relative lack of plasticity of the two most extreme populations, our findings are consistent with a scenario of a locally adaptive stress response syndrome in high elevation populations. Due to a reduced phenotypic plasticity, an overall low intra‐population genetic diversity of the adaptive traits and weak gene flow, populations of high altitude might have difficulties to cope with, e.g. a rise of temperature.
Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF σ factor and cognate Ser/Thr kinase
Authors: Bayer‐Santos Ethel , Lima Lídia dos Passos , Ceseti Lucas de Moraes , Ratagami Camila Yuri , de Santana Eliane Silva , da Silva Aline Maria , Farah Chuck Shaker , Alvarez‐Martinez Cristina Elisa
Published: February 2018

Plant‐associated bacteria of the genus Xanthomonas cause disease in a wide range of economically important crops. However, their ability to persist in the environment is still poorly understood. Predation by amoebas represents a major selective pressure to bacterial populations in the environment. In this study, we show that the X. citri type 6 secretion system (T6SS) promotes resistance to predation by the soil amoeba Dictyostelium discoideum. We found that an extracytoplasmic function (ECF) sigma factor (EcfK) is required for induction of T6SS genes during interaction with Dictyostelium. EcfK homologues are found in several environmental bacteria in association with a gene encoding a eukaryotic‐like Ser/Thr kinase (pknS). Deletion of pknS causes sensitivity to amoeba predation and abolishes induction of T6SS genes. Phosphomimetic mutagenesis of EcfK identified a threonine residue (T51) that renders EcfK constitutively active in standard culture conditions. Moreover, susceptibility of ΔpknS to Dictyostelium predation can be overcome by expression of the constitutively active version EcfKT51E from a multicopy plasmid. Together, these results describe a new regulatory cascade in which PknS functions through activation of EcfK to promote T6SS expression. Our work reveals an important aspect of Xanthomonas physiology that affects its ability to persist in the environment.
The politics of international redistribution: Explaining public support for fiscal transfers in the EU
Authors: KLEIDER HANNA , STOECKEL FLORIAN
Published: February 2018

As a consequence of the Eurozone crisis and the creation of the European Stability Mechanism (ESM), the prospect of a transfer union has become a particularly contested aspect of European integration. How should one understand the public backlash against fiscal transfers? And, what explains voter preferences for international transfers more generally? Using data from the 2014 European Elections Study (EES), this article describes the first cross‐national analysis of voters’ preferences on international transfers. The analysis reveals a strong association between voters’ non‐economic cultural orientations (i.e., their cosmopolitanism) and their position on transfers. At the same time, it is found that voters’ economic left‐right orientations are crucial for a fuller understanding of the public conflict over transfers. This counters previous research that finds economic left‐right orientations to be of little explanatory value. This study demonstrates that the association between economic left‐right orientations and preferences for international transfers is conditional on a person's social class. Among citizens in a high‐income class an economically left‐leaning position is associated with support for transfers, whereas it is associated with opposition to transfers among citizens in a low‐income class.
When parasitoids deal with the spatial distribution of their hosts: consequences for both partners
Authors: Louâpre Philippe , Le Lann Cécile , Hance Thierry
Published: February 2018

Insect parasitoids developing inside hosts face a true challenge: hosts are scattered in the field and their localization and selection require the use of complex and sometime confusing information. It was assumed for a long time that small‐brained organisms like parasitoids have evolved simple and efficient behavioral mechanisms, leading them to be adapted to a given ecological situation, for example, the spatial distribution of hosts in the habitat. However, hosts are not static and their distribution may also vary through generations and within the life of parasitoid individuals. We investigated if and how parasitoids deal with such a spatial complexity in a mesocosm experiment. We used theAphidius rhopalosiphi/Sitobion avenaeparasitoid/host system to investigate if parasitoid females experiencing different host aggregation levels exhibit different foraging behaviors independently of the number of hosts in the environment. We showed thatA. rhopalosiphifemales exploited hosts more intensively both within and among patches at higher host aggregation levels. We discussed the adaptiveness of such behaviors in the light of evolution and biological control.
Inactivation of Escherichia Coli O157:H7 and Listeria Innocua by Benzoic Acid, Ethylenediaminetetraacetic Acid and Their Combination in Model Wash Water and Simulated Spinach Washing
Authors: Alborzi Solmaz , Bastarrachea Luis J. , Ding Qiao , Tikekar Rohan V.
Published: February 2018

An antimicrobial effect of benzoic acid (BA) and ethylenediaminetetraacetic acid (EDTA) was evaluated as a potential antimicrobial treatment against Escherichia coli O157:H7 and Listeria innocua. A 30 min exposure to the combination of 15 mM BA and 1 mM EDTA at 22 °C resulted in approximately 3 logarithmic reductions in stationary phase E. coli O157:H7. Logarithmic phase E. coli O157:H7 was more sensitive (P < 0.05) to the treatment and 1 mM EDTA alone caused more than 5 logarithmic reductions. L. innocua was also sensitive to a treatment with 15 mM BA alone, which induced 5 logarithmic reductions. By increasing the temperature of the solution containing 15 mM BA and 1 mM EDTA to 40 °C, more than 5 logarithmic reductions in stationary phase E. coli O157:H7 was observed after 5 min of treatment. However, the antimicrobial effect was attenuated (reaching less than 1 logarithmic reductions) at 4 °C. In addition, the combined BA and EDTA treatment retained its antimicrobial effect against E. coli O157:H7 for at least 6 cycles of treatment over 6 days at room temperature (22 °C). In a simulated spinach washing study, 15 mM BA and 1 mM EDTA together were able to prevent cross‐contamination of E. coli O157:H7. The results highlight the potential use of combination of BA (15 mM) and EDTA (1 mM) to address microbial risk from E. coli O157:H7 and L. innocua in fresh produce industry.

Practical Application

This study demonstrates the effectiveness of benzoic acid (BA) and EDTA mixture in inactivating bacteria in the water used for produce washing and reducing the incidence of cross‐contamination during washing of fresh produce. Use of BA + EDTA mixture has significant benefits such as: (a) ability to be reused, (b) effectiveness in the presence of organic matter, and (c) reduced need of monitoring wash water conditions such as pH, concentration and organic matter.
Aerated Steam Sanitization of Whole Fresh Cantaloupes Reduces and Controls Rind‐Associated Listeria but Enhances Fruit Susceptibility to Secondary Colonization
Authors: Bezanson Greg S. , Ells Timothy C. , Fan Lihua , Forney Charles F. , LeBlanc Denyse I.
Published: February 2018

Recent bacterial illnesses and outbreaks associated with the consumption of fresh and fresh‐cut fruit and vegetables emphasize the need to supply produce that is microbiologically safe while retaining its quality and nutrient value. We assessed the capacity of aerated steam to reduce initial levels and control the posttreatment proliferation of a 4‐strain mixture of Listeria innocua, a surrogate for L. monocytogenes, and microflora native to the rind of whole cantaloupes. Studies were conducted at the pilot‐scale level by passing deliberately contaminated melons through a prototype stainless‐steel, continuous‐feed heating device. Exposure for 240 s to aerated steam heated to 85 °C achieved a mean reduction in surface‐inoculated L. innocua of 3.9 ± 0.6 log10 CFU/cm2 (n = 3) and decreased background microorganisms (yeast, moulds, and coliforms) to undetectable levels. No significant outgrowth of surviving L. innocua or yeast and moulds was observed on heat‐treated melons during their storage at 4, 7, and 10 °C for 14 days. Treated fruit continued to respire. Although rind quality was altered, edible fleshy portions remained largely unaffected. Cantaloupe inoculated with L. innocua subsequent to its exposure to aerated steam provided a suitable environment for surrogate growth (mean 3.3 log10 increase in rind density over 10 days at 7 °C), whereas its proliferation was restricted on nonheated cantaloupe (mean 0.7 log10 increase). Steam sanitization provides an effective means for the control of pathogen and spoilage organisms, but the proliferation of surrogate organisms on heated cantaloupes raises concern regarding the impact of postprocessing contamination on consumer health risk.

Practical Application

Water vapor (steam) at a high temperature can be used to sanitize the surface of fresh, whole cantaloupe melons in a continuous‐feed manner. Both Listeria bacteria and spoilage organisms are markedly reduced from initial levels and survivor outgrowth severely restricted during subsequent refrigerated storage. This approach to microorganism control is likely most applicable in situations where rinds and flesh are to be separated immediately via further processing.
Effects of microRNA‐133b on retinal vascular endothelial cell proliferation and apoptosis through angiotensinogen‐mediated angiotensin II‐ extracellular signal‐regulated kinase 1/2 signalling pathway in rats with diabetic retinopathy
Authors: Liu Tao‐Tao , Hao Qian , Zhang Yan , Li Zhao‐Hui , Cui Zhi‐Hua , Yang Wei
Published: February 2018

Purpose

This study aimed to explore the effects of microRNA‐133b (miR‐133b) on diabetic retinopathy (DR) by targeting angiotensinogen (AGT) through the angiotensin‐II (AngII) extracellular signal‐regulated kinase 1/2 (ERK1/2) signalling pathway in rats.

Methods

The DR rat model was established using retinal tissues of DR rats and normal rats. Immunohistochemistry was performed to detect the protein expressions of AGT and CD34 in retinal tissues. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blotting were applied to detect miR‐133b expression, AGT, AngII, ERK1/2 mRNA, and protein expressions in tissues and cells after transfection. Retinal vascular endothelial cells were cultured and divided into normal, blank, miR‐133b mimics, miR‐133b mimics negative control (NC), miR‐133b inhibitors, miR‐133b inhibitors NC, siRNA NC, siRNA‐AGT, and miR‐133b inhibitors + siRNA‐AGT groups. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay was performed to detect cell proliferation. Cell cycle and apoptosis were evaluated using flow cytometry.

Results

Compared with normal rats, AGT and CD34 were expressed more frequently in DR rats. MicroRNA (miR)‐133b expression was downregulated but AGT, AngII, ERK1 and ERK2 mRNA expressions were upregulated in retinal tissues of DR rats. When compared to the normal group, all other groups displayed decreased cell proliferation, increased cell number in G0/G1, decreased cell number in S stage, increased cell apoptosis rate and declined miR‐133b expression. As well, significant increased expressions of AGT and the AngII‐ERK1/2 pathway‐related proteins were observed in retinal vascular endothelial cells in all groups except the normal group. The miR‐133b mimics and siRNA‐AGT groups had increased cell proliferation, decreased cell number in the G0/G1 phase, increased cell number in S stage, decreased cell apoptosis rate and decreased expressions of AGT and AngII‐ERK1/2 pathway‐related proteins than the miR‐133b inhibitors + siRNA‐AGT group. The miR‐133b inhibitors group exhibited opposite trends compared with the miR‐133b mimics and siRNA‐AGT groups.

Conclusion

The study provides data to suggest that miR‐133b induces proliferation and inhibits apoptosis of retinal vascular endothelial cells by targeting AGT through the AngII‐ERK1/2 signalling pathway in DR rats.
Urinary, bowel and sexual health in older men from Northern Ireland
Authors: Donnelly David W. , Donnelly Conan , Kearney Therese , Weller David , Sharp Linda , Downing Amy , Wilding Sarah , Wright Penny , Kind Paul , Catto James W.F. , Cross William R. , Mason Malcolm D. , McCaughan Eilis , Wagland Richard , Watson Eila , Mottram Rebecca , Allen Majorie , Butcher Hugh , Hounsome Luke , Selby Peter , Huws Dyfed , Brewster David H. , McNair Emma , Rivas Carol , Nayoan Johana , Horton Mike , Matheson Lauren , Glaser Adam W. , Gavin Anna
Published: February 2018

Objectives

To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population.

Subjects and Methods

A cross‐sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age‐matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ‐5D‐5L) and 26‐item Expanded Prostate Cancer Composite (EPIC‐26) instruments were used to enable comparisons with prostate cancer outcome studies. Whilst representative of the prostate cancer survivor population, the age‐distribution of the sample differs from the general population, thus data were generalised to the NI population by excluding those aged 40–59 years and applying survey weights. Results are presented as proportions reporting problems along with mean composite scores, with differences by respondent characteristics assessed using chi‐squared tests, analysis of variance, and multivariable log‐linear regression.

Results

Amongst men aged ≥60 years, 32.8% reported sexual dysfunction, 9.3% urinary dysfunction, and 6.5% bowel dysfunction. In all, 38.1% reported at least one problem and 2.1% all three. Worse outcome was associated with increasing number of long‐term conditions, low physical activity, and higher body mass index (BMI). Urinary incontinence, urinary irritation/obstruction, and sexual dysfunction increased with age; whilst urinary incontinence, bowel, and sexual dysfunction were more common among the unemployed.

Conclusion

These data provide an insight into sensitive issues seldom reported by elderly men, which result in poor general health, but could be addressed given adequate service provision. The relationship between these problems, raised BMI and low physical activity offers the prospect of additional health gain by addressing public health issues such as obesity. The results provide essential contemporary population data against which outcomes for those living with prostate cancer can be compared. They will facilitate greater understanding of the true impact of specific treatments such as surgical interventions, pelvic radiation or androgen‐deprivation therapy.
Ebselen has lithium‐like effects on central 5‐HT2A receptor function
Authors: Antoniadou I , Kouskou M , Arsiwala T , Singh N , Vasudevan S R , Fowler T , Cadirci E , Churchill G C , Sharp T
Published: February 2018

Background and Purpose

Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in Gq‐protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5‐HT2A receptor, a Gq‐protein coupled receptor involved in lithium's actions.

Experimental Approach

5‐HT2A receptor function was assessed in mice by measuring the behavioural (head‐twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c‐fos, Egr2) responses to 5‐HT2A receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5‐HT2A receptor function. Because lithium and 5‐HT2A receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co‐administration with the SSRI citalopram in microdialysis (extracellular 5‐HT) experiments.

Key Results

Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5‐HT2A receptor agonist DOI. Repeated lithium also inhibited DOI‐evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L‐690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR‐A014418) did not. Finally, ebselen enhanced the increase in extracellular 5‐HT induced by citalopram, and also increased regional brain 5‐HT synthesis.

Conclusions and Implications

Our data demonstrated lithium‐mimetic effects of ebselen in different experimental models of 5‐HT2A receptor function, probably mediated by IMPase inhibition. This evidence of lithium‐like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent.
Decorin‐mediated oncosuppression – a potential future adjuvant therapy for human epithelial cancers
Authors: Sainio Annele Orvokki , Järveläinen Hannu Tapio
Published: February 2018

Currently, the multifaceted role of the extracellular matrix (ECM) in tumourigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumourigenesis is decorin, the prototype of the small leucine‐rich proteoglycan gene family. The actions of decorin include its ability to function as an endogenous pan‐receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail. We also provide a summary of preclinical studies exploring the value of decorin‐mediated oncosuppression, as a potential future adjuvant therapy for epithelial cancers.

Linked Articles

This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc
Monoclonal antibodies against metzincin targets
Authors: Santamaria Salvatore , de Groot Rens
Published: February 2018

The metzincin clan of metalloproteinases includes the MMP, disintegrin and metalloproteinase (ADAM) and ADAM with thrombospondin motifs families, which cleave extracellular targets in a wide range of (patho)physiological processes. Antibodies constitute a powerful tool to modulate the activity of these enzymes for both therapeutic and research purposes. In this review, we give an overview of monoclonal antibodies (mAbs) that have been tested in preclinical disease models, human trials and important studies of metzincin structure and function. Initial attempts to develop therapeutic small molecule inhibitors against MMPs were hampered by structural similarities between metzincin active sites and, consequently, off‐target effects. Therefore, more recently, mAbs have been developed that do not bind to the active site but bind to surface‐exposed loops that are poorly conserved in closely related family members. Inhibition of protease activity by these mAbs occurs through a variety of mechanisms, including (i) barring access to the active site, (ii) disruption of exosite binding, and (iii) prevention of protease activation. These different modes of inhibition are discussed in the context of the antibodies' potency, selectivity and, importantly, the effects in models of disease and clinical trials. In addition, various innovative strategies that were used to generate anti‐metzincin mAbs are discussed.

Linked Articles

This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc
The stepwise development of the lamprey visual system and its evolutionary implications
Authors: Suzuki Daichi G. , Grillner Sten
Published: February 2018

Lampreys, which represent the oldest group of living vertebrates (cyclostomes), show unique eye development. The lamprey larva has only eyespot‐like immature eyes beneath a non‐transparent skin, whereas after metamorphosis, the adult has well‐developed image‐forming camera eyes. To establish a functional visual system, well‐organised visual centres as well as motor components (e.g. trunk muscles for locomotion) and interactions between them are needed. Here we review the available knowledge concerning the structure, function and development of the different parts of the lamprey visual system. The lamprey exhibits stepwise development of the visual system during its life cycle. In prolarvae and early larvae, the ‘primary’ retina does not have horizontal and amacrine cells, but does have photoreceptors, bipolar cells and ganglion cells. At this stage, the optic nerve projects mostly to the pretectum, where the dendrites of neurons in the nucleus of the medial longitudinal fasciculus (nMLF) appear to receive direct visual information and send motor outputs to the neck and trunk muscles. This simple neural circuit may generate negative phototaxis. Through the larval period, the lateral region of the retina grows again to form the ‘secondary’ retina and the topographic retinotectal projection of the optic nerve is formed, and at the same time, the extra‐ocular muscles progressively develop. During metamorphosis, horizontal and amacrine cells differentiate for the first time, and the optic tectum expands and becomes laminated. The adult lamprey then has a sophisticated visual system for image‐forming and visual decision‐making. In the adult lamprey, the thalamic pathway (retina–thalamus–cortex/pallium) also transmits visual stimuli. Because the primary, simple light‐detecting circuit in larval lamprey shares functional and developmental similarities with that of protochordates (amphioxus and tunicates), the visual development of the lamprey provides information regarding the evolutionary transition of the vertebrate visual system from the protochordate‐type to the vertebrate‐type.