bluuebunny/crossref_metadata_2025 huggingface dataset:
Conflict monitoring and adaptation as reflected by N2 amplitude in obsessive–compulsive disorder
Authors: Riesel A. , Klawohn J. , Kathmann N. , Endrass T.
Published: January 2017

Background

Feelings of doubt and perseverative behaviours are key symptoms of obsessive–compulsive disorder (OCD) and have been linked to hyperactive error and conflict signals in the brain. While enhanced neural correlates of error monitoring have been robustly shown, far less is known about conflict processing and adaptation in OCD.

Method

We examined event-related potentials during conflict processing in 70 patients with OCD and 70 matched healthy comparison participants, focusing on the stimulus-locked N2 elicited in a flanker task. Conflict adaptation was evaluated by analysing sequential adjustments in N2 and behaviour, i.e. current conflict effects as a function of preceding conflict.

Results

Patients with OCD showed enhanced N2 amplitudes compared with healthy controls. Further, patients showed stronger conflict adaptation effects on reaction times and N2 amplitude. Thus, the effect of previous compatibility was larger in patients than in healthy participants as indicated by greater N2 adjustments in change trials (i.e. iC, cI). As a result of stronger conflict adaptation in patients, N2 amplitudes were comparable between groups in incompatible trials following incompatible trials.

Conclusions

Larger N2 amplitudes and greater conflict adaptation in OCD point to enhanced conflict monitoring leading to increased recruitment of cognitive control in patients. This was most pronounced in change trials and was associated with stronger conflict adjustment in N2 and behaviour. Thus, hyperactive conflict monitoring in OCD may be beneficial in situations that require a high amount of control to resolve conflict, but may also reflect an effortful process that is linked to distress and symptoms of OCD.
Two Trajectories in the Neolithization of Eurasia: Pottery Versus Agriculture (Spatiotemporal Patterns)
Authors: Kuzmin Yaroslav V
Published: January 2017

Data on the emergence of pottery and agriculture in Eurasia were analyzed from the view of their spatiotemporal relationship. It was found that there are 2 major types of association between pottery and agriculture: 1) East Asian, with pottery as the main criterion of the Neolithization; and 2) Levantine, with agriculture as the phenomenon most closely related to the emergence of the Neolithic. Some regions of Eurasia have intermediate characteristics. The concept of a single area for pottery origin in eastern Eurasia and its subsequent spread to the west, still used by some scholars, is the revival of the old diffusionist paradigm and does not seem to advance the analysis of the Neolithization process. If the wheat/barley agriculture definitely originated in the Levantine “core” and spread toward Anatolia and central/western Europe, it is impossible to apply the same approach to pottery. The latest developments in chronology of the earliest ceramics in China, one of the key regions in the world in terms of the origin of pottery-making, are critically evaluated.
Implications for Deriving Regional Fossil Fuel CO2 Estimates from Atmospheric Observations in a Hot Spot of Nuclear Power Plant 14CO2 Emissions
Authors: Vogel Felix R , Levin Ingeborg , Worthy Doug E J
Published: January 2017

Using Δ14C observations to infer the local concentration excess of CO2 due to the burning of fossil fuels (ΔFFCO2) is a promising technique to monitor anthropogenic CO2 emissions. A recent study showed that 14CO2 emissions from the nuclear industry can significantly alter the local atmospheric 14CO2 concentration and thus mask the Δ14C depletion due to ΔFFCO2. In this study, we investigate the relevance of this effect for the vicinity of Toronto, Canada, a hot spot of anthropogenic 14CO2 emissions. Comparing the measured emissions from local power plants to a global emission inventory highlighted significant deviations on interannual timescales. Although the previously assumed emission factor of 1.6 TBq(GWa)-1 agrees with the observed long-term average for all CANDU reactors of 1.50 ± 0.18 TBq(GWa)-1. This power-based parameterization neglects the different emission ratios for individual reactors, which range from 3.4 ± 0.82 to 0.65 ± 0.09 TBq(GWa)-1. This causes a mean difference of-14% in 14CO2 concentrations in our simulations at our observational site in Egbert, Canada. On an annual time basis, this additional 14CO2 masks the equivalent of 27–82% of the total annual FFCO2 offset. A pseudo-data experiment suggests that the interannual variability in the masked fraction may cause spurious trends in the ΔFFCO2 estimates of the order of 30% from 2006–2010. In addition, a comparison of the modeled Δ14C levels with our observational time series from 2008–2010 underlines that incorporating the best available 14CO2 emissions significantly increases the agreement. There were also short periods with significant observed Δ14C offsets, which were found to be linked with maintenance periods conducted on these nuclear reactors.
Altitudinal filtering of large-tree species explains above-ground biomass variation in an Atlantic Central African rain forest
Authors: Gonmadje Christelle , Picard Nicolas , Gourlet-Fleury Sylvie , Réjou-Méchain Maxime , Freycon Vincent , Sunderland Terry , McKey Doyle , Doumenge Charles
Published: January 2017

Patterns in above-ground biomass of tropical forests over short altitudinal gradients are poorly known. The aim of this study was to investigate the variation of above-ground biomass with altitude in old-growth forests and determine the importance of changes in floristic composition as a cause of this variation. We used a dataset from 15 1-ha permanent plots established from lowland (200 m asl) to submontane forests (900 m asl) in the Ngovayang Massif, south-western Cameroon. We analysed variation over altitude in two specific functional traits, the potential maximum tree height and the wood density. Forest above-ground biomass decreased from 500–600 Mg ha−1 in lowland plots to around 260 Mg ha−1 at the highest altitudes. The contribution to above-ground biomass of large-tree species (dbh ≥ 70 cm) decreased with altitude, while the contribution of smaller trees was constant. Contribution of the Fabaceae subfamily Caesalpinioideae decreased with altitude, while those of Clusiaceae, Phyllanthaceae and Burseraceae increased. While potential maximum tree height significantly decreased, wood specific gravity displayed no trend along the gradient. Finally, the decrease in above-ground biomass along the short altitudinal gradient can be at least partially explained by a shift in species composition, with large-tree species being filtered out at the highest altitudes. These results suggest that global change could lead to significant shifts in the properties of montane forests over time.
The contributions of Albert W. Hull to X-ray powder diffraction at one hundred years of his landmark publication
Authors: Delgado José Miguel
Published: January 2017

One hundred years ago X-ray powder diffraction, one of the premier techniques used in the characterization of materials, was invented. Its origins can be traced to two landmark contributions presented to the scientific community in 1916. They are the better known and celebrated work carried out by Paul Scherrer under the guidance of Peter W. Debye, at the University of Göttingen, Germany, and the lesser known work of Albert W. Hull performed at the Research Laboratory of the General Electric Company, Schenectady, NY, USA. The great contributions of Scherrer and Debye have been prominently recognized. They are presented in many textbooks and in technical and scientific articles published in the area of characterization of materials using powder diffraction techniques. The camera designed by them, later called “the Debye–Scherrer camera”, was used extensively for many years and the experimental setup (“the Debye–Scherrer geometry”) is still used today. On the other hand, the work performed by Hull has not been adequately appreciated and remembered. In this communication, an account of his contributions to X-ray powder diffraction and to crystallography is presented at 100 years of his landmark publication, which appeared in the first issue of Physical Review of 1917.
The Effect of Ambulance Staffing Models in a Metropolitan, Fire-Based EMS System
Authors: Cortez Eric J. , Panchal Ashish R. , Davis James E. , Keseg David P.
Published: January 2017

Introduction

The staffing of ambulances with different levels of Emergency Medical Service (EMS) providers is a difficult decision with evidence being mixed on the benefit of each model.

Hypothesis/Problem

The objective of this study was to describe a pilot program evaluating alternative staffing on two ambulances utilizing the paramedic-basic (PB) model (staffed with one paramedic and one emergency medical technician[EMT]).

Methods

This was a retrospective study conducted from September 17, 2013 through December 31, 2013. The PB ambulances were compared to geographically matched ambulances staffed with paramedic-paramedic (PP ambulances). One PP and one PB ambulance were based at Station A; one PP and one PB ambulance were based at Station B. The primary outcome was total on-scene time. Secondary outcomes included time-to-electrocardiogram (EKG), time-to-intravenous (IV) line insertion, IV-line success rate, and percentage of protocol violations. Inclusion criteria were all patients requesting prehospital services that were attended to by these teams. Patients were excluded if they were not attended to by the study ambulance vehicles. Descriptive statistics were reported as medians and interquartile ranges (IQR). Proportions were reported with 95% confidence intervals (CI). The Mann-Whitley U test was used for significance testing (P<.05).

Results

Median on-scene times at Station A for the PP ambulance were shorter than the PB ambulance team (PP: 10.1 minutes, IQR 6.0-15; PB: 13.0 minutes, IQR 8.1-18; P=.01). This finding also was noted at Station B (PP: 13.5 minutes, IQR 8.5-19; PB: 14.3 minutes, IQR 9.9-20; P=.01). There were no differences between PP and PB ambulance teams at Station A or Station B in time-to-EKG, time-to-IV insertion, IV success rate, and protocol violation rates.

Conclusion

In the setting of a well-developed EMS system utilizing an all-Advanced Life Support (ALS) response, this study suggests that PB ambulance teams may function well when compared to PP ambulances. Though longer scene times were observed, differences in time to ALS interventions and protocol violation rates were not different. Hybrid ambulance teams may be an effective staffing alternative, but decisions to use this model must address clinical and operational concerns.

CortezEJ, PanchalAR, DavisJE, KesegDP. The effect of ambulance staffing models in a metropolitan, fire-based EMS system. Prehosp Disaster Med. 2017;32(2):175–179.
The unstoppable glottal: tracking rapid change in an iconic British variable
Authors: SMITH JENNIFER , HOLMES-ELLIOTT SOPHIE
Published: January 2017

This article presents a sociolinguistic investigation of a rapidly expanding innovation in the UK, glottal replacement, in a variety spoken in northeast Scotland. Quantitative analysis of the form shows a dramatic change in apparent time: from a minority variant in the older generation to a full 90 per cent use in the younger generation. Further analysis of the constraints on use provide a detailed snapshot of how this variant moves through social and linguistic space. Males use higher rates of the non-standard form in the older generations but this constraint is neutralised in the younger generations as the form increases. Styleshifting according to interlocutor also neutralises through time. While these results across the social constraints are in line with previous analyses, the linguistic constraints differ in this variety. In contrast to most other varieties, intervocalic contexts such asbottleshow high rates of glottal replacement. Moreover, word-internal foot-initial contexts (e.g.sometimes) also frequently allow the non-standard variant, despite this being rare in other dialects. Although glottal replacement is largely considered to be a ‘torchbearer’ of geographical diffusion, this in-depth analysis suggests that different varieties may have different pathways of change in the rapid transition from [t] to [ʔ] throughout the UK.
Association of neighbourhood food availability with the consumption of processed and ultra-processed food products by children in a city of Brazil: a multilevel analysis
Authors: Leite Fernanda Helena Marrocos , de Carvalho Cremm Elena , de Abreu Débora Silva Costa , Oliveira Maria Aparecida de , Budd Nadine , Martins Paula Andrea
Published: January 2017

Objective

To investigate the association between neighbourhood food availability and the consumption of ready-to-consume products (RCP), either processed or ultra-processed, and unprocessed/minimally processed foods (UF-MPF) by children.

Design

Cross-sectional. 24 h Dietary recalls were collected from children from January 2010 to June 2011. Neighbourhood food availability data were collected from 672 food stores located within 500 m of participants’ homes, using an adapted and validated instrument. Neighbourhood-level socio-economic status (SES) was obtained by calculating the mean years of household head’s education level in each census tract covered by 500 m buffers. Foods that were consumed by children and/or available in the food stores were classified based on their degree of industrial processing. Multilevel random-effect models examined the association between neighbourhood food availability and children’s diets.

Setting

Santos, Brazil.

Subjects

Children (n513) under 10 years old (292 aged <6 years, 221 aged ≥6 years).

Results

The availability of RCP in food stores was associated with increased RCP consumption (P<0·001) and decreased UF-MPF consumption (P<0·001). The consumption of UF-MPF was positively associated with neighbourhood-level SES (P<0·01), but not with the availability of UF-MPF in the neighbourhood.

Conclusions

Results suggest that food policies and interventions that aim to reduce RCP consumption in Santos and similar settings should focus on reducing the availability in food stores. The results also suggest that interventions should not only increase the availability of UF-MPF in lower-SES neighbourhoods, but should strive to make UF-MPF accessible within these environments.
Radiation-induced biological changes of neural structures in the base of the skull tumours
Authors: Buzea C. Gh. , Mirestean C. , Butuc Irina , Zara A. , Iancu D. T.
Published: January 2017

Background and purpose

The aim of this paper is to compare neural induced changes in three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for nasopharyngeal cancers.

Materials and methods

Radiotherapy plans for 10 patients with nasopharyngeal cancer stages III and IV were prospectively developed for 3D-CRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. Normal tissue complication probabilities were calculated.

Results

The mean planning target volume’s (PTVs) conformity index (CI) for 3D-CRT was 1·424, for IMRT 1·1, and for VMAT 1·081. The PTV homogeneity (HI) index was 0·204 for 3D-CRT, 0·124 for IMRT and 0·153 for VMAT. Normal tissue complication probabilities gave complex results for 3D-CRT, IMRT and VMAT and are analysed in detail in this paper. The mean monitor units were 95 (range 9–180) for 3D-CRT; 165 (range 52–277) for IMRT; and 331 (range 167–494) for VMAT (p<0·05).

Conclusions

VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for nasopharyngeal cancer. VMAT is associated with faster delivery times and greater number of mean monitor units than IMRT. Brain radionecrosis severity and risk, in the past, have been underestimated. By improving the life expectancy of patients with nasopharyngeal cancer to ensure maintenance of the neural structures, recommended dose limits should be considered as a first degree priority (as the spinal cord, brainstem, etc.) when IMRT and VMAT plans are implemented.
Sleep disturbances in caregivers of patients with advanced cancer: A systematic review.
Authors: Maltby Kirstin F. , Sanderson Christine R. , Lobb Elizabeth A. , Phillips Jane L.
Published: January 2017

Objective:

Sleep disturbances are a common issue for those who provide informal care to someone with a life-limiting condition. The negative consequences of poor sleep are well documented. The purpose of the present study was to determine the sleep patterns of caregivers of patients with advanced cancer.

Method:

An extensive systematic review of studies reporting empirical sleep data was undertaken in 2015 in accordance with the PRISMA Statement. A total of eight electronic databases were searched, with no date restrictions imposed. Additionally, a search of the bibliographies of the studies identified during the electronic search was conducted. Search terms included: “sleep,” “insomnia,” “sleep disturbance,” “circadian rhythm,” “caregiver,” “carer,” “advanced cancer,” “palliative cancer,” and MESH suggestions. The inclusion criteria required studies to be in English and to report primary qualitative and/or quantitative research that examined sleep in caregivers of patients with advanced cancer. Unpublished studies, conference papers, and dissertations were excluded.

Results:

Overall, 10 studies met the inclusion criteria and were included in the review. Two major findings emerged from the data synthesis. First, at least 72% of caregivers reported moderate to severe sleep disturbance as measured by the Pittsburgh Sleep Quality Index. Second, objective measurement of caregivers' sleep identified that some caregivers experienced up to a 44% reduction in their total sleep time compared to the recommended eight hours.

Significance of Results:

Reduction in total sleep time appears to be the biggest issue facing caregivers' sleep. Future studies need to explore the specific factors that cause these sleep disturbances and thus help to identify interventions to optimize sleep.
HILLARY CLINTON AND THE WOMEN WHO SUPPORTED HER
Authors: Simien Evelyn M. , Hampson Sarah Cote
Published: January 2017

Using data from the 2008 American National Election Studies (ANES) time series, and the 2008 ANES panel wave, this study examines whether the intragroup emotions Hillary Clinton elicits—gender affinity and pride—are predictive of political engagement for the group she represents: women voters. We focus on voters who report having participated in the primaries and the range of potential voters who proselytize during the primary season and express an intention to vote in the general election. Contrary to the conclusion one might reasonably draw—that is, women rather than men would be more likely to support Clinton—the real question is:whichwomen?
Standard-setting activities and new institutional economics
Authors: MAZÉ ARMELLE
Published: January 2017

From a New Institutional Economics (NIE) perspective, standards are acknowledged to play a central role in building efficient market infrastructure by defining what is exchanged and reducing the level of transaction and measurement costs. Nevertheless, only a few prior NIE studies have considered standard-setting activities as coordination and governance issuesper se. This article aims to fill this gap by adapting and extending the classical Williamsonian analytical framework to the governance of standard-setting institutions. This analysis is substantiated by empirical data on global private standards in the agricultural sector. Our results highlight the importance of standard selection and the limits to current harmonisation as regards institutional failure to define alternative multilateral governance mechanisms at the international level.
Design of ultra compact dual-band bandpass filter using L-shaped resonator
Authors: Pourasad Yeganeh , Karimi Gholamreza
Published: January 2017

A compact dual-band microstrip bandpass filter (BPF) is presented for application at the frequencies 2.4 and 5.84 GHz. The proposed main resonator consists of two L-shaped resonators. To improve the upper-stopband of the proposed filter, modified U-Shaped resonators are accepted. The operation mechanism of the filter is investigated based on proffered equivalent-circuit model and transformation function. The sketched dual-band BPF attends the insertion loss less than 0.1 and 0.4 dB Also the return loss is 26 and 28 dB at 2.4 and 5.84, respectively. This proffered filter structure is proper for Bluetooth and wireless local area networks and other wireless communication systems. An overall good agreement between measured and simulated results is observed.
The role of marriage in criminal recidivism: a longitudinal and co-relative analysis
Authors: Kendler K. S. , Lönn S. L. , Sundquist J. , Sundquist K.
Published: January 2017

Aims.

Marriage is associated with a reduced rate of criminal recidivism, but the underlying mechanisms have only partly been elucidated. We seek to clarify the nature of the association between marriage and recidivism and how that relationship may be moderated as a function of gender, deviance of spouse, a history of violence and familial risk.

Method.

We utilise a longitudinal cohort design consisting of Swedish men (n = 239 328) and women (n = 72 280), born between 1958 and 1986, who were convicted of at least one crime before age 20 and were not married prior to age 20. The analyses used Cox regression with marriage as a time-dependent covariate. We also perform co-relative analyses in sibling and first cousin pairs.

Results.

Marriage after a first crime substantially reduces risk of recidivism in both males (hazard ratio (HR) with key covariates and 95% confidence intervals 0.55, 0.53–0.57) and females (HR = 0.38, 0.34–0.42), although the effect is stronger in females. Marriage to a deviant spouse increases recidivism rates in males. In males, a history of violent criminality and high familial risk, respectively, decrease and increase sensitivity to the protective effect of marriage on recidivism. Consistent with a causal effect of marriage on recidivism, marriage was associated with a decline in risk for criminal relapse comparable with that in the population in both male–male sibling pairs (raw HR = 0.53, 0.45–0.62) and cousin pairs (HR = 0.55, 0.47, 0.65) concordant for prior convictions.

Conclusions.

The protective effect of marriage on risk for criminal recidivism is likely largely causal and is of importance in both males and females. Those at high familial risk for criminal behaviour are more sensitive to the protective effects of marriage.
Investigating the Negation of Media Stereotypes
Authors: Arendt Florian
Published: January 2017

Abstract. We investigated the negation of media stereotypes. Negation refers to an internal attempt to negate stereotypic content (“No! This is not true!”). The process of negation is important because a critical assessment of stereotypic content can be beneficial for stereotype and prejudice reduction. This fact is a crucial reason why readers’ disagreement regarding simplified stereotypic depictions is of central interest for mass communication research and media literacy campaigns. Importantly, factors that can increase negation are of special interest. Although the ability and motivation to process stereotypic content can be theoretically identified as potential influencing factors, media-stereotype research has not yet tested the influence of these factors on negation. In Experiment 1 ( N = 347), we manipulated the motivation to negate by presenting awareness material. We informed some of the participants that the news media often do not represent the world as it is, but sometimes do so in a stereotypic way. Analyses revealed that participants who received the awareness material before reading negated to a higher extent. In Experiment 2 ( N = 223), we investigated the impact of ability by manipulating the time participants had to negate stereotypic content. The ability to negate was assumed to be higher the more time the participants had to process stereotypic information. As hypothesized, negation was higher when there was more time available. Interestingly, the increase in effect size was dampened the more time was available, which indicated a curvilinear relationship. Implications for media-literacy campaigns are discussed.
Report Calls for Revised Method to Chart Cost of Climate Change
Authors: Showstack Randy
Published: January 2017

Proposed changes could improve the calculation's scientific basis and transparency, according to the report.
Annual time-series analysis of aqueous eDNA reveals ecologically relevant dynamics of lake ecosystem biodiversity
Authors: Bista Iliana , Carvalho Gary R. , Walsh Kerry , Seymour Mathew , Hajibabaei Mehrdad , Lallias Delphine , Christmas Martin , Creer Simon
Published: January 2017

The use of environmental DNA (eDNA) in biodiversity assessments offers a step-change in sensitivity, throughput and simultaneous measures of ecosystem diversity and function. There remains, however, a need to examine eDNA persistence in the wild through simultaneous temporal measures of eDNA and biota. Here, we use metabarcoding of two markers of different lengths, derived from an annual time series of aqueous lake eDNA to examine temporal shifts in ecosystem biodiversity and in an ecologically important group of macroinvertebrates (Diptera: Chironomidae). The analyses allow different levels of detection and validation of taxon richness and community composition (β-diversity) through time, with shorter eDNA fragments dominating the eDNA community. Comparisons between eDNA, community DNA, taxonomy and UK species abundance data further show significant relationships between diversity estimates derived across the disparate methodologies. Our results reveal the temporal dynamics of eDNA and validate the utility of eDNA metabarcoding for tracking seasonal diversity at the ecosystem scale.
Infrared laser-induced gene expression for tracking development and function of single C. elegans embryonic neurons
Authors: Singhal Anupriya , Shaham Shai
Published: January 2017

Visualizing neural-circuit assembly in vivo requires tracking growth of optically resolvable neurites. The Caenorhabditis elegans embryonic nervous system, comprising 222 neurons and 56 glia, is attractive for comprehensive studies of development; however, embryonic reporters are broadly expressed, making single-neurite tracking/manipulation challenging. We present a method, using an infrared laser, for reproducible heat-dependent gene expression in small sublineages (one to four cells) without radiation damage. We go beyond proof-of-principle, and use our system to label and track single neurons during early nervous-system assembly. We uncover a retrograde extension mechanism for axon growth, and reveal the aetiology of axon-guidance defects in sax-3/Robo and vab-1/EphR mutants. We also perform cell-specific rescues, determining DAF-6/patched-related site of action during sensory-organ development. Simultaneous ablation and labelling of cells using our system reveals roles for glia in dendrite extension. Our method can be applied to other optically/IR-transparent organisms, and opens the door to high-resolution systematic analyses of C. elegans morphogenesis.
Human farnesyl pyrophosphate synthase is allosterically inhibited by its own product
Authors: Park Jaeok , Zielinski Michal , Magder Alexandr , Tsantrizos Youla S. , Berghuis Albert M.
Published: January 2017

Farnesyl pyrophosphate synthase (FPPS) is an enzyme of the mevalonate pathway and a well-established therapeutic target. Recent research has focused around a newly identified druggable pocket near the enzyme’s active site. Pharmacological exploitation of this pocket is deemed promising; however, its natural biological function, if any, is yet unknown. Here we report that the product of FPPS, farnesyl pyrophosphate (FPP), can bind to this pocket and lock the enzyme in an inactive state. The Kd for this binding is 5–6 μM, within a catalytically relevant range. These results indicate that FPPS activity is sensitive to the product concentration. Kinetic analysis shows that the enzyme is inhibited through FPP accumulation. Having a specific physiological effector, FPPS is a bona fide allosteric enzyme. This allostery offers an exquisite mechanism for controlling prenyl pyrophosphate levels in vivo and thus contributes an additional layer of regulation to the mevalonate pathway.
Structural basis of ligand interaction with atypical chemokine receptor 3
Authors: Gustavsson Martin , Wang Liwen , van Gils Noortje , Stephens Bryan S. , Zhang Penglie , Schall Thomas J. , Yang Sichun , Abagyan Ruben , Chance Mark R. , Kufareva Irina , Handel Tracy M.
Published: January 2017

Chemokines drive cell migration through their interactions with seven-transmembrane (7TM) chemokine receptors on cell surfaces. The atypical chemokine receptor 3 (ACKR3) binds chemokines CXCL11 and CXCL12 and signals exclusively through β-arrestin-mediated pathways, without activating canonical G-protein signalling. This receptor is upregulated in numerous cancers making it a potential drug target. Here we collected over 100 distinct structural probes from radiolytic footprinting, disulfide trapping, and mutagenesis to map the structures of ACKR3:CXCL12 and ACKR3:small-molecule complexes, including dynamic regions that proved unresolvable by X-ray crystallography in homologous receptors. The data are integrated with molecular modelling to produce complete and cohesive experimentally driven models that confirm and expand on the existing knowledge of the architecture of receptor:chemokine and receptor:small-molecule complexes. Additionally, we detected and characterized ligand-induced conformational changes in the transmembrane and intracellular regions of ACKR3 that elucidate fundamental structural elements of agonism in this atypical receptor.
Imperfect two-dimensional topological insulator field-effect transistors
Authors: Vandenberghe William G. , Fischetti Massimo V.
Published: January 2017

To overcome the challenge of using two-dimensional materials for nanoelectronic devices, we propose two-dimensional topological insulator field-effect transistors that switch based on the modulation of scattering. We model transistors made of two-dimensional topological insulator ribbons accounting for scattering with phonons and imperfections. In the on-state, the Fermi level lies in the bulk bandgap and the electrons travel ballistically through the topologically protected edge states even in the presence of imperfections. In the off-state the Fermi level moves into the bandgap and electrons suffer from severe back-scattering. An off-current more than two-orders below the on-current is demonstrated and a high on-current is maintained even in the presence of imperfections. At low drain-source bias, the output characteristics are like those of conventional field-effect transistors, at large drain-source bias negative differential resistance is revealed. Complementary n- and p-type devices can be made enabling high-performance and low-power electronic circuits using imperfect two-dimensional topological insulators.
One million years of glaciation and denudation history in west Greenland
Authors: Strunk Astrid , Knudsen Mads Faurschou , Egholm David L. , Jansen John D. , Levy Laura B. , Jacobsen Bo H. , Larsen Nicolaj K.
Published: January 2017

The influence of major Quaternary climatic changes on growth and decay of the Greenland Ice Sheet, and associated erosional impact on the landscapes, is virtually unknown beyond the last deglaciation. Here we quantify exposure and denudation histories in west Greenland by applying a novel Markov-Chain Monte Carlo modelling approach to all available paired cosmogenic 10Be-26Al bedrock data from Greenland. We find that long-term denudation rates in west Greenland range from >50 m Myr−1 in low-lying areas to ∼2 m Myr−1 at high elevations, hereby quantifying systematic variations in denudation rate among different glacial landforms caused by variations in ice thickness across the landscape. We furthermore show that the present day ice-free areas only were ice covered ca. 45% of the past 1 million years, and even less at high-elevation sites, implying that the Greenland Ice Sheet for much of the time was of similar size or even smaller than today.
Efficient DNA-free genome editing of bread wheat using CRISPR/Cas9 ribonucleoprotein complexes
Authors: Liang Zhen , Chen Kunling , Li Tingdong , Zhang Yi , Wang Yanpeng , Zhao Qian , Liu Jinxing , Zhang Huawei , Liu Cuimin , Ran Yidong , Gao Caixia
Published: January 2017

Substantial efforts are being made to optimize the CRISPR/Cas9 system for precision crop breeding. The avoidance of transgene integration and reduction of off-target mutations are the most important targets for optimization. Here, we describe an efficient genome editing method for bread wheat using CRISPR/Cas9 ribonucleoproteins (RNPs). Starting from RNP preparation, the whole protocol takes only seven to nine weeks, with four to five independent mutants produced from 100 immature wheat embryos. Deep sequencing reveals that the chance of off-target mutations in wheat cells is much lower in RNP mediated genome editing than in editing with CRISPR/Cas9 DNA. Consistent with this finding, no off-target mutations are detected in the mutant plants. Because no foreign DNA is used in CRISPR/Cas9 RNP mediated genome editing, the mutants obtained are completely transgene free. This method may be widely applicable for producing genome edited crop plants and has a good prospect of being commercialized.
Molecular Characterization of Pediatric Restrictive Cardiomyopathy from Integrative Genomics
Authors: Rindler Tara N. , Hinton Robert B. , Salomonis Nathan , Ware Stephanie M.
Published: January 2017

Pediatric restrictive cardiomyopathy (RCM) is a genetically heterogeneous heart disease with limited therapeutic options. RCM cases are largely idiopathic; however, even within families with a known genetic cause for cardiomyopathy, there is striking variability in disease severity. Although accumulating evidence implicates both gene expression and alternative splicing in development of dilated cardiomyopathy (DCM), there have been no detailed molecular characterizations of underlying pathways dysregulated in RCM. RNA-Seq on a cohort of pediatric RCM patients compared to other forms of adult cardiomyopathy and controls identified transcriptional differences highly common to the cardiomyopathies, as well as those unique to RCM. Transcripts selectively induced in RCM include many known and novel G-protein coupled receptors linked to calcium handling and contractile regulation. In-depth comparisons of alternative splicing revealed splicing events shared among cardiomyopathy subtypes, as well as those linked solely to RCM. Genes identified with altered alternative splicing implicate RBM20, a DCM splicing factor, as a potential mediator of alternative splicing in RCM. We present the first comprehensive report on molecular pathways dysregulated in pediatric RCM including unique/shared pathways identified compared to other cardiomyopathy subtypes and demonstrate that disruption of alternative splicing patterns in pediatric RCM occurs in the inverse direction as DCM.
Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction
Authors: Huang Sheng-Teng , Huang Chao-Chun , Huang Wen-Liang , Lin Tsu-Kung , Liao Pei-Lin , Wang Pei-Wen , Liou Chia-Wei , Chuang Jiin-Haur
Published: January 2017

Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells both in vitro and in vivo. Administration of Tan IIA to NOD-SCID mice implanted with 143B cells led to significant inhibition of tumor development. The inhibition of proliferation, migration, and invasion was observed in 143B cells treated with Tan IIA. The tumor proliferation markers, Ki67 and PCNA, were suppressed and apoptosis by TUNEL assay was activated respectively. Apoptosis in the Tan IIA-treated 143B cells and xerograft mice was associated with the activation of caspase cascade via the modulation of Bcl-2 family. The CD31 was inhibited in Tan IIA-treated xenografts to indicate anti-neovasculization. Tan IIA administration resulted in a significant decrease in the mitochondrial fusion proteins, Mfn1/2 and Opa1, as well as an increase in the fission protein Drp1. We concluded that mitochondrial dysfunction associated with dynamic change was involved in apoptosis and anti-angiogenesis elicited by Tan IIA.
Combination of mometasone furoate and oxymetazoline for the treatment of adenoid hypertrophy concomitant with allergic rhinitis: A randomized controlled trial
Authors: Liu Wenlong , Zhou Lifeng , Zeng Qingxiang , Luo Renzhong
Published: January 2017

In the clinic, approximately 30% of children with adenoid hypertrophy (AH) concomitant with allergic rhinitis (AR) report poor responses to intranasal steroids. To determine whether the combination of mometasone furoate (MF) and oxymetazoline (OXY) is more effective than either agent alone, we performed a two-stage, parallel, randomized, double-blind, double-dummy, clinical trial with 240 AH children with concomitant perennial AR. During the first stage, all children were randomly assigned to the MF or control group for six weeks of treatment. During the second stage, the non-responders from stage one were randomly assigned to 4 groups for 8 weeks of treatment that involved receiving the following treatments: MF/OXY, MF/placebo, placebo/OXY, or placebo/placebo. During the first stage of treatment, 39% of the responders treated with MF achieved greater reductions in total and individual symptom scores than did those on placebo. During the second stage of treatment, the nasal congestion scores of the MF/OXY group significantly decreased. The adenoid/choana ratio of the MF/OXY-treated group decreased and the nasal volume increased significantly. Our results suggest that the combination of OXY and MF is effective and safe for the treatment of AH children with concomitant AR and has a rapid onset of action.
A salivary EF-hand calcium-binding protein of the brown planthopper Nilaparvata lugens functions as an effector for defense responses in rice
Authors: Ye Wenfeng , Yu Haixin , Jian Yukun , Zeng Jiamei , Ji Rui , Chen Hongdan , Lou Yonggen
Published: January 2017

The brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), a major pest of rice in Asia, is able to successfully puncture sieve tubes in rice with its piercing stylet and then to ingest phloem sap. How BPH manages to continuously feed on rice remains unclear. Here, we cloned the gene NlSEF1, which is highly expressed in the salivary glands of BPH. The NlSEF1 protein has EF-hand Ca2+-binding activity and can be secreted into rice plants when BPH feed. Infestation of rice by BPH nymphs whose NlSEF1 was knocked down elicited higher levels of Ca2+ and H2O2 but not jasmonic acid, jasmonoyl-isoleucine (JA-Ile) and SA in rice than did infestation by control nymphs; Consistently, wounding plus the recombination protein NlSEF1 suppressed the production of H2O2 in rice. Bioassays revealed that NlSEF1-knockdown BPH nymphs had a higher mortality rate and lower feeding capacity on rice than control nymphs. These results indicate that the salivary protein in BPH, NlSEF1, functions as an effector and plays important roles in interactions between BPH and rice by mediating the plant’s defense responses.
Profiling single-guide RNA specificity reveals a mismatch sensitive core sequence
Authors: Zheng Ting , Hou Yingzi , Zhang Pingjing , Zhang Zhenxi , Xu Ying , Zhang Letian , Niu Leilei , Yang Yi , Liang Da , Yi Fan , Peng Wei , Feng Wenjian , Yang Ying , Chen Jianxin , Zhu York Yuanyuan , Zhang Li-He , Du Quan
Published: January 2017

Targeting specificity is an essential issue in the development of CRISPR-Cas technology. Using a luciferase activation assay, off-target cleavage activity of sgRNA was systematically investigated on single nucleotide-mismatched targets. In addition to confirming that PAM-proximal mismatches are less tolerated than PAM-distal mismatches, our study further identified a “core” sequence that is highly sensitive to target-mismatch. This sequence is of 4-nucleotide long, located at +4 to +7 position upstream of PAM, and positioned in a steric restriction region when assembled into Cas9 endonuclease. Our study also found that, single or multiple target mismatches at this region abolished off-target cleavage mediated by active sgRNAs, thus proposing a principle for gene-specific sgRNA design. Characterization of a mismatch sensitive “core” sequence not only enhances our understanding of how this elegant system functions, but also facilitates our efforts to improve targeting specificity of a sgRNA.
The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina
Authors: Rolandelli A. , Hernández Del Pino R. E. , Pellegrini J. M. , Tateosian N. L. , Amiano N. O. , de la Barrera S. , Casco N. , Gutiérrez M. , Palmero D. J. , García V. E.
Published: January 2017

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.
Continuous cell supply from Krt7-expressing hematopoietic stem cells during native hematopoiesis revealed by targeted in vivo gene transfer method
Authors: Tajima Yoko , Ito Keiichi , Umino Ayumi , Wilkinson Adam C. , Nakauchi Hiromitsu , Yamazaki Satoshi
Published: January 2017

The nature of hematopoietic stem cells under normal hematopoiesis remained largely unknown due to the limited assays available to monitor their behavior in situ. Here, we develop a new mouse model to transfer genes specifically into the primitive hematopoietic stem cell compartment through the utilization of a modified Rcas/TVA system. We succeeded in transferring a GFP reporter gene into adult hematopoietic stem cells in vivo, which are predominantly quiescent, by generating pseudotyped-lentivirus. Furthermore, we demonstrate the utility of this system to study neonatal hematopoiesis, a developmental stage that has been difficult to analyze to date. Using the system developed in this study, we observed continuous multi-lineage hematopoietic cell supply in peripheral blood from Krt7-positive hematopoietic stem cells during unperturbed homeostatic condition. This powerful experimental system could provide a new standard tool to analyze hematopoiesis under physiological condition without transplantation.
An extraordinary palaeontinid from the Triassic of Korea and its significance
Authors: Nam Kye Soo , Wang Ying , Ren Dong , Kim Jong Heon , Szwedo Jacek
Published: January 2017

A new, extraordinary palaeontinid Hallakkungis amisanus Nam, Wang & Szwedo, gen. et sp. nov., from the Upper Triassic of the Amisan Formation in Boryeong City, Korea is described. It is the first Palaeontinidae from Korea. The newly described taxon displays a mosaic of characters present in presumed ancestors of this insect family and some highly advanced features.
Characterization of a P1-like bacteriophage carrying CTX-M-27 in Salmonella spp. resistant to third generation cephalosporins isolated from pork in China
Authors: Yang Ling , Li Wan , Jiang Gui-Ze , Zhang Wen-Hui , Ding Huan-Zhong , Liu Ya-Hong , Zeng Zhen-Ling , Jiang Hong-Xia
Published: January 2017

The aim of this study was to elucidate the epidemiology of third generation cephalosporin resistant Samonella isolates from pork of a slaughterhouse in China and the features of transferable elements carrying blaCTX-M genes. One hundred and twenty-six (7.3%) Salmonella isolates were identified; S. Derby and S. Rissen were the most two prevalent serotypes. Among these isolates 20 (15.8%) were resistant to third generation cephalosporins and nine of them carried blaCTX-M-27. S1-PFGE and replicon typing of blaCTX-M-27-carrying plasmids showed that seven were untypeable plasmids of about 104 Kb and two were IncP plasmids of about 300 Kb. Complete sequence analysis of one PBRT-untypeable plasmid showed it was a P1-like bateriophage, named SJ46, which contained a non-phage-associated region with several mobile elements, including Tn1721, ISEcp1B and IS903D. The other six 104 Kb PBRT-untypeable blaCTX-M-27-carrying plasmids also harboured the same phage-insertion region of SJ46 suggesting that they were the same P1-like bacteriophage. PFGE profiles of the parental strains revealed both potential vertical and horizontal spread of this P1-like blaCTX-M-27-containing element. Additionally, the representative gene of the P1 family bacteriophage, repL, was detected in 19.0% (24/126) of the isolates. This study indicated a potential role of P1-family bacteriophage in capture and spread of antimicrobial resistance in pathogens.
Wearable Atmospheric Pressure Plasma Fabrics Produced by Knitting Flexible Wire Electrodes for the Decontamination of Chemical Warfare Agents
Authors: Jung Heesoo , Seo Jin Ah , Choi Seungki
Published: January 2017

One of the key reasons for the limited use of atmospheric pressure plasma (APP) is its inability to treat non-flat, three-dimensional (3D) surface structures, such as electronic devices and the human body, because of the rigid electrode structure required. In this study, a new APP system design—wearable APP (WAPP)—that utilizes a knitting technique to assemble flexible co-axial wire electrodes into a large-area plasma fabric is presented. The WAPP device operates in ambient air with a fully enclosed power electrode and grounded outer electrode. The plasma fabric is flexible and lightweight, and it can be scaled up for larger areas, making it attractive for wearable APP applications. Here, we report the various plasma properties of the WAPP device and successful test results showing the decontamination of toxic chemical warfare agents, namely, mustard (HD), soman (GD), and nerve (VX) agents.