bluuebunny/crossref_metadata_2025 huggingface dataset:
Wine, Women, Men, and Type II Error
Authors: Bodington Jeffrey C.
Published: May 2017

More than forty published works show that women and men differ in their taste preferences for sweet, salt, sour, bitter, fruit, and other flavors. Despite those differences, dozens of state fair and other wine competitions determine winners' ribbons, medals, scores, and ranks by pooling the opinions of female and male judges. This article examines twenty-three blind wine tastings during which female and male judges scored more than nine hundred wines. Two-sample t-test results show that the gender-specific distributions of scores do have similar means and standard deviations. Exact p-values for two-sample chi-square tests show that the distributions of men's and women's scores are not significantly different, and exact p-values for likelihood ratio tests of Plackett-Luce model results show that the genders' preference orders are not significantly different. The correlation coefficient between women's and men's scores is weakly positive in 90 percent of the tastings. On that evidence, indications that the genders prefer different wines are difficult to detect. If such differences do exist, as the nonwine literature implies, the results of this analysis show that those differences are small compared to non-gender-related idiosyncratic differences between individuals and random expressions of preference. The potential for accept-a-false-null-hypothesis Type II error when pooling female and male judges' wine-related opinions appears to be small. (JEL Classifications: A10, C10, C00, C12, D12)
Post-secular identity in contemporary Italian cinema: Catholic ‘cement’, the suppression of history and the lost Islamic other
Authors: Brook Clodagh
Published: May 2017

Alessandro Ferrari claims that Catholicism was the only cement binding the newly unified Italy together, a country without a common language or a widespread culture capable of founding civic engagement. Taking a post-secular perspective on religion, which recognizes that religion is not simply a ‘residue’ soon to be extinguished (as Raymond Williams once stated), this article will explore Italian cinema’s contemporary constructions of this national ‘religious cement’ as a putative foundation for identity in 21st century Italy. The article sets out too to show the cracks in the cement: collective identity can only be created by ignoring religious diversity and removing thorny issues from the history of the Catholic church.
Decreased, but still sufficient, iodine intake of children and adults in the Netherlands
Authors: Verkaik-Kloosterman Janneke , Buurma-Rethans Elly J. M. , Dekkers Arnold L. M. , van Rossum Caroline T. M.
Published: May 2017

Sufficient I intake is important for the synthesis of thyroid hormones, which play an important role in normal growth and development. Our aim was to estimate habitual I intake for the Dutch population and the risk of inadequate or excessive intakes. Further, we aimed to provide an insight into the dietary sources of I and the association with socio-demographic factors. Data from the Dutch National Food Consumption Survey 2007–2010 (n3819; 7–69 years), and from the Dutch food and supplement composition tables were used to estimate habitual I intake with a calculation model. Contribution of food groups to I intake were computed and multiple linear regression was used to examine associations of intakes with socio-demographic factors. A total of ≤2 % of the population had an intake below the estimated average requirement or above the upper level. The main sources of I were bread containing iodised salt (39 %), dairy products (14 %) and non-alcoholic drinks (6 %). I intake (natural sources only, excluding iodised salt and supplements) was positively associated with (parental) education, which could at least partly be attributed to a higher consumption of dairy products. Among children, the consumption of bread, often containing iodised bakery salt, was positively associated with parental education. The I intake of the Dutch population (7–69 years) seems adequate, although it has decreased since the period before 2008. With the current effort to reduce salt intake and changing dietary patterns (i.e. less bread, more organic foods) it is important to keep a close track on the I status, important sources and potential risk groups.
EVALUATION CRITERIA OF PATIENT AND PUBLIC INVOLVEMENT IN RESOURCE ALLOCATION DECISIONS: A LITERATURE REVIEW AND QUALITATIVE STUDY
Authors: Rosenberg-Yunger Zahava R.S. , Bayoumi Ahmed M.
Published: May 2017

Objectives: We developed specific evaluation criteria to assess patient and public involvement in resource allocation decisions in health care.

Methods: We reviewed the literature from health and other sectors relevant to stakeholder involvement and conducted twenty-seven key informant interviews with stakeholders knowledgeable about patient and public involvement in Canadian drug resource allocation decisions. We used an inductive qualitative thematic approach to analyze the interviews with codes and categories developed directly from individuals’ interview transcripts.

Results: Integrating respondents’ comments and the literature review, we identified nine evaluation criteria of patient and the public involvement in healthcare resource allocation decision making: clarity regarding rationale and roles of patient and public members, sufficient support, adequate representation of relevant views, fair decision-making processes, legitimacy of committee processes, adequate opportunity for participation, meaningful degree of participation, noticeable effect on decisions, and considerations of the efficiency of patient and public involvement.

Conclusions: Our results will help to develop methods to evaluate patient and public involvement in healthcare decision making.
G-NETWORKS AND THEIR APPLICATIONS TO MACHINE LEARNING, ENERGY PACKET NETWORKS AND ROUTING: INTRODUCTION TO THE SPECIAL ISSUE
Authors: Caglayan Mehmet Ufuk
Published: May 2017

This paper introduces a special issue of this journal (Probability in the Engineering and Informational Sciences) that is devoted to G(elenbe)-Networks and their Applications. The special issue is based on revised versions of some of the papers that were presented at a workshop held in early January 2017 at the Séminaire Saint-Paul in Nice (France). It includes contributions in several research directions that followed from the introduction of the G-Network in the late 1980s. The papers present original theoretical developments, as well as applications of G-Networks to Machine Learning, to the performance optimization of energy systems via the novelEnergy Packet Networksformalism for systems that operate with renewable and intermittent energy sources, and to packet network routing and Cloud management over the Internet. We introduce these contributions from the perspective of an overview of recent work based on G-Networks.
Girls’ and boys’ trajectories of appearance anxiety from age 10 to 15 years are associated with earlier maturation and appearance-related teasing
Authors: Zimmer-Gembeck Melanie J. , Webb Haley J. , Farrell Lara J. , Waters Allison M.
Published: May 2017

Adolescents’ appearance-related concerns can provoke increasing emotional, social, and eating-related problems. The aims of this five-wave (2.5-year), multiple-informant longitudinal study were to (a) examine growth trajectories of appearance anxiety symptoms and appearance esteem, (b) identify whether trajectories differed by gender, and (c) examine several launching factors including parent-reported physical maturation, peer-rated physical appearance, body mass index, and appearance teasing by parents and peers. Participants were 387 adolescents (44% boys) aged 10 to 13 years at the first assessment. Steep growth in appearance anxiety symptoms was found for both girls and boys, but there was no average change in appearance esteem. Girls had more elevated appearance anxiety symptoms and lower appearance esteem than boys, girls’ body mass index was associated with symptoms, and earlier physical maturation and teasing about appearance, alone and in combination, were associated with growth in appearance anxiety symptoms for girls and boys. Earlier maturing boys who were highly teased by parents, but even more so when teased by peers, were at utmost risk for elevated appearance anxiety symptoms and increasing symptoms over time. In contrast, all girls exhibited elevated or increasing appearance anxiety symptoms across time, with the exception of girls with the latest maturation who also reported little teasing about their appearance.
Predictors of health-related quality of life in children with chronic heart disease
Authors: Niemitz Mandy , Gunst Diana C. M. , Hövels-Gürich Hedwig H. , Hofbeck Michael , Kaulitz Renate , Galm Christoph , Berger Felix , Nagdyman Nicole , Stiller Brigitte , Borth-Bruhns Thomas , Konzag Ines , Balmer Christian , Goldbeck Lutz
Published: May 2017

Objective

Chronic paediatric heart disease is often associated with residual symptoms, persisting functional restrictions, and late sequelae for psychosocial development. It is, therefore, increasingly important to evaluate the health-related quality of life of children and adolescents with chronic heart disease. The aim of this study was to determine medical and socio-demographic variables affecting health-related quality of life in school-aged children and adolescents with chronic heart disease.

Patients and methods

The Pediatric Cardiac Quality of Life Inventory was administered to 375 children and adolescents and 386 parental caregivers. Medical information was obtained from the charts. The socio-demographic information was provided by the patients and caregivers.

Results

Greater disease severity, low school attendance, current cardiac medication, current parental employment, uncertain or limited prognosis, history of connection to a heart–lung machine, number of nights spent in a hospital, and need for treatment in a paediatric aftercare clinic independently contributed to lower health-related quality of life (self-report: R2=0.41; proxy-report: R2=0.46). High correlations between self-reports and parent-proxy reports indicated concordance regarding the evaluation of a child’s health-related quality of life.

Conclusions

Beyond medical treatment, integration into school is important to increase health-related quality of life in children and adolescents surviving with chronic heart disease. Regular screening of health-related quality of life is recommended to identify patients with special needs.
Multiple Resistance to Glyphosate and Acetolactate Synthase Inhibitors in Palmer Amaranth (Amaranthus palmeri) Identified in Brazil
Authors: Küpper Anita , Borgato Ednaldo A. , Patterson Eric L. , Gonçalves Netto Acácio , Nicolai Marcelo , Carvalho Saul J. P. de , Nissen Scott J. , Gaines Todd A. , Christoffoleti Pedro J.
Published: May 2017

Palmer amaranth is native to the United States, but was discovered in 2015 in Brazil. Palmer amaranth populations in Brazil were very difficult to control using glyphosate, which resulted in many changes to standard weed management practices. A genotyping assay was used to confirm that the population detected in Mato Grosso State, Brazil, was correctly identified as Palmer amaranth and that it was not tall waterhemp. Greenhouse dose–response curves and shikimate accumulation assays showed that the Brazilian population was highly resistant to glyphosate, with an LD50 value (3,982 g glyphosate ha−1) more than twice the typical use rates and very little shikimate accumulation at 1 mM glyphosate concentrations in a leaf-disk assay. The Brazilian population was also resistant to sulfonylurea and imidazolinone acetolactate synthase (ALS) inhibitor herbicides. The resistance mechanisms in the Brazilian population were identified as increasedEPSPSgene copy number for glyphosate resistance (between 50- and 179-fold relativeEPSPSgene copy number increase) and two different alleles for target-site mutations in theALSgene (W574L and S653N). These results confirm the introduction of Palmer amaranth to Brazil using a genetic marker for species identification, as well as resistance to glyphosate and ALS inhibitors.
Survivin, a key player in cancer progression, increases in obesity and protects adipose tissue stem cells from apoptosis
Authors: Ejarque Miriam , Ceperuelo-Mallafré Victòria , Serena Carolina , Pachón Gisela , Núñez-Álvarez Yaiza , Terrón-Puig Margarida , Calvo Enrique , Núñez-Roa Catalina , Oliva-Olivera Wilfredo , Tinahones Francisco J , Peinado Miguel Angel , Vendrell Joan , Fernández-Veledo Sonia
Published: May 2017

Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin. Within AT, survivin was primarily detected in human adipocyte-derived stem cells (hASCs), the adipocyte precursors that determine AT expansion. Remarkably, survivin expression was significantly higher in hASCs isolated from obese patients that from lean controls and was increased by proinflammatory M1 macrophage soluble factors including IL-1β. Analysis of survivin expression in hASCs revealed a complex regulation including epigenetic modifications and protein stability. Surprisingly, obese hASCs showed survivin promoter hypermethylation that correlated with a significant decrease in its mRNA levels. Nonetheless, a lower level of mir-203, which inhibits survivin protein translation, and higher protein stability, was found in obese hASCs compared with their lean counterparts. We discovered that survivin levels determine the susceptibility of hASCs to apoptotic stimuli (including leptin and hypoxia). Accordingly, hASCs from an obese setting were protected from apoptosis. Collectively, these data shed new light on the molecular mechanisms governing AT expansion in obesity through promotion of hASCs that are resistant to apoptosis, and point to survivin as a potential new molecular player in the communication between AT and tumor cells. Thus, inhibition of apoptosis targeting survivin might represent an effective strategy for both obesity and cancer therapy.
Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer
Authors: Xiao Lu , Lan Xiaoying , Shi Xianping , Zhao Kai , Wang Dongrui , Wang Xuejun , Li Faqian , Huang Hongbiao , Liu Jinbao
Published: May 2017

Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat non-small cell lung cancer (NSCLC) but NSCLC develops resistance to the agent, limiting therapeutic efficacy. Despite many approaches to identifying the underlying mechanism for cisplatin resistance, there remains a lack of effective targets in the population that resist cisplatin treatment. In this study, we sought to investigate the role of cytoplasmic RAP1, a previously identified positive regulator of NF-κB signaling, in the development of cisplatin resistance in NSCLC cells. We found that the expression of cytoplasmic RAP1 was significantly higher in high-grade NSCLC tissues than in low-grade NSCLC; compared with a normal pulmonary epithelial cell line, the A549 NSCLC cells exhibited more cytoplasmic RAP1 expression as well as increased NF-κB activity; cisplatin treatment resulted in a further increase of cytoplasmic RAP1 in A549 cells; overexpression of RAP1 desensitized the A549 cells to cisplatin, and conversely, RAP1 depletion in the NSCLC cells reduced their proliferation and increased their sensitivity to cisplatin, indicating that RAP1 is required for cell growth and has a key mediating role in the development of cisplatin resistance in NSCLC cells. The RAP1-mediated cisplatin resistance was associated with the activation of NF-κB signaling and the upregulation of the antiapoptosis factor BCL-2. Intriguingly, in the small portion of RAP1-depleted cells that survived cisplatin treatment, no induction of NF-κB activity and BCL-2 expression was observed. Furthermore, in established cisplatin-resistant A549 cells, RAP1 depletion caused BCL2 depletion, caspase activation and dramatic lethality to the cells. Hence, our results demonstrate that the cytoplasmic RAP1–NF-κB–BCL2 axis represents a key pathway to cisplatin resistance in NSCLC cells, identifying RAP1 as a marker and a potential therapeutic target for cisplatin resistance of NSCLC.
MicroRNA-23b functions as an oncogene and activates AKT/GSK3β/β-catenin signaling by targeting ST7L in hepatocellular carcinoma
Authors: Zhuang Likun , Wang Xin , Wang Zusen , Ma Xiang , Han Bing , Zou Hao , Wu Zehua , Dong Sheng , Qu Zhiqiang , Zang Yunjin , Wu Liqun
Published: May 2017

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3β/β-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.
Unified model for singlet fission within a non-conjugated covalent pentacene dimer
Authors: Basel Bettina S. , Zirzlmeier Johannes , Hetzer Constantin , Phelan Brian T. , Krzyaniak Matthew D. , Reddy S. Rajagopala , Coto Pedro B. , Horwitz Noah E. , Young Ryan M. , White Fraser J. , Hampel Frank , Clark Timothy , Thoss Michael , Tykwinski Rik R. , Wasielewski Michael R. , Guldi Dirk M.
Published: May 2017

When molecular dimers, crystalline films or molecular aggregates absorb a photon to produce a singlet exciton, spin-allowed singlet fission may produce two triplet excitons that can be used to generate two electron–hole pairs, leading to a predicted ∼50% enhancement in maximum solar cell performance. The singlet fission mechanism is still not well understood. Here we report on the use of time-resolved optical and electron paramagnetic resonance spectroscopy to probe singlet fission in a pentacene dimer linked by a non-conjugated spacer. We observe the key intermediates in the singlet fission process, including the formation and decay of a quintet state that precedes formation of the pentacene triplet excitons. Using these combined data, we develop a single kinetic model that describes the data over seven temporal orders of magnitude both at room and cryogenic temperatures.
High conductance values in π-folded molecular junctions
Authors: Carini Marco , Ruiz Marta P. , Usabiaga Imanol , Fernández José A. , Cocinero Emilio J. , Melle-Franco Manuel , Diez-Perez Ismael , Mateo-Alonso Aurelio
Published: May 2017

Folding processes play a crucial role in the development of function in biomacromolecules. Recreating this feature on synthetic systems would not only allow understanding and reproducing biological functions but also developing new functions. This has inspired the development of conformationally ordered synthetic oligomers known as foldamers. Herein, a new family of foldamers, consisting of an increasing number of anthracene units that adopt a folded sigmoidal conformation by a combination of intramolecular hydrogen bonds and aromatic interactions, is reported. Such folding process opens up an efficient through-space charge transport channel across the interacting anthracene moieties. In fact, single-molecule conductance measurements carried out on this series of foldamers, using the scanning tunnelling microscopy-based break-junction technique, reveal exceptionally high conductance values in the order of 10−1G0 and a low length decay constant of 0.02 Å−1 that exceed the values observed in molecular junctions that make use of through-space charge transport pathways.
Genetic architecture of epigenetic and neuronal ageing rates in human brain regions
Authors: Lu Ake T. , Hannon Eilis , Levine Morgan E. , Crimmins Eileen M. , Lunnon Katie , Mill Jonathan , Geschwind Daniel H. , Horvath Steve
Published: May 2017

Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10−9) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10−20). Locus 1p36.12 is significantly associated (P=2.2 × 10−8) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P=1.4 × 10−12), ulcerative colitis (P<1.0 × 10−20), type 2 diabetes (P=2.8 × 10−13), hip/waist circumference in men (P=1.1 × 10−9), schizophrenia (P=1.6 × 10−9), cognitive decline (P=5.3 × 10−4) and Parkinson’s disease (P=8.6 × 10−3).
Nanometric holograms based on a topological insulator material
Authors: Yue Zengji , Xue Gaolei , Liu Juan , Wang Yongtian , Gu Min
Published: May 2017

Holography has extremely extensive applications in conventional optical instruments spanning optical microscopy and imaging, three-dimensional displays and metrology. To integrate holography with modern low-dimensional electronic devices, holograms need to be thinned to a nanometric scale. However, to keep a pronounced phase shift modulation, the thickness of holograms has been generally limited to the optical wavelength scale, which hinders their integration with ultrathin electronic devices. Here, we break this limit and achieve 60 nm holograms using a topological insulator material. We discover that nanometric topological insulator thin films act as an intrinsic optical resonant cavity due to the unequal refractive indices in their metallic surfaces and bulk. The resonant cavity leads to enhancement of phase shifts and thus the holographic imaging. Our work paves a way towards integrating holography with flat electronic devices for optical imaging, data storage and information security.
The origin and degassing history of the Earth's atmosphere revealed by Archean xenon
Authors: Avice Guillaume , Marty Bernard , Burgess Ray
Published: May 2017

Xenon (Xe) is an exceptional tracer for investigating the origin and fate of volatile elements on Earth. The initial isotopic composition of atmospheric Xe remains unknown, as do the mechanisms involved in its depletion and isotopic fractionation compared with other reservoirs in the solar system. Here we present high precision analyses of noble gases trapped in fluid inclusions of Archean quartz (Barberton, South Africa) that reveal the isotopic composition of the paleo-atmosphere at ≈3.3 Ga. The Archean atmospheric Xe is mass-dependently fractionated by 12.9±2.4 ‰ u−1 (± 2σ, s.d.) relative to the modern atmosphere. The lower than today 129Xe excess requires a degassing rate of radiogenic Xe from the mantle higher than at present. The primordial Xe component delivered to the Earth's atmosphere is distinct from Solar or Chondritic Xe but similar to a theoretical component called U-Xe. Comets may have brought this component to the Earth's atmosphere during the last stages of terrestrial accretion.
Physical activity and risk of comorbidities in patients with chronic obstructive pulmonary disease: a cohort study
Authors: Yu Tsung , ter Riet Gerben , Puhan Milo A. , Frei Anja
Published: May 2017

Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor. The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients. The study included 409 patients from primary care practice in the Netherlands and Switzerland. We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years. During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment. We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis. Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity. However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75–0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79–1.00; p = 0.045). In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time. Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiety.
Towards new cholera prophylactics and treatment: Crystal structures of bacterial enterotoxins in complex with GM1 mimics
Authors: Heggelund Julie Elisabeth , Mackenzie Alasdair , Martinsen Tobias , Heim Joel Benjamin , Cheshev Pavel , Bernardi Anna , Krengel Ute
Published: May 2017

Cholera is a life-threatening disease in many countries, and new drugs are clearly needed. C-glycosidic antagonists may serve such a purpose. Here we report atomic-resolution crystal structures of three such compounds in complexes with the cholera toxin. The structures give unprecedented atomic details of the molecular interactions and show how the inhibitors efficiently block the GM1 binding site. These molecules are well suited for development into low-cost prophylactic drugs, due to their relatively easy synthesis and their resistance to glycolytic enzymes. One of the compounds links two toxin B-pentamers in the crystal structure, which may yield improved inhibition through the formation of toxin aggregates. These structures can spark the improved design of GM1 mimics, either alone or as multivalent inhibitors connecting multiple GM1-binding sites. Future developments may further include compounds that link the primary and secondary binding sites. Serving as decoys, receptor mimics may lessen symptoms while avoiding the use of antibiotics.
Angiopoietin-1 enhances neutrophil chemotaxis in vitro and migration in vivo through interaction with CD18 and release of CCL4
Authors: Burnett Amanda , Gomez Ingrid , De Leon David Davila , Ariaans Mark , Progias Pavlos , Kammerer Richard A. , Velasco Guillermo , Marron Marie , Hellewell Paul , Ridger Victoria
Published: May 2017

Angiopoietins are a family of growth factors that are ligands for the tyrosine kinase receptor, Tie2. Angiopoietin 1 (Ang-1) is agonistic for Tie2, plays a key role in blood vessel maturation and stability and has been shown to possess anti-inflammatory properties. However, Tie2 expression has been demonstrated on human neutrophils and the observation that neutrophils migrate in response to Ang-1in vitrohas confounded research into its exact role in inflammation as well as its potential use as a therapeutic agent. We used a mouse model of peritoneal neutrophilic inflammation to determine if Ang-1 could stimulate neutrophil migrationin vivo. Tie2 expression was demonstrated on mouse neutrophils. In addition, recombinant human Ang-1 induced significant chemotaxis of isolated mouse neutrophils in a Tie2- and CD18-dependent manner. Subsequently, co-immunoprecipitation of Ang-1 and CD18 demonstrated their interaction. Intraperitoneal injection of an engineered angiopoietin-1, MAT.Ang-1, induced significant neutrophil migration into the peritoneum and a significant increase in the levels of CCL4 in peritoneal lavage fluid. Depletion of resident peritoneal macrophages prior to, or concomitant injections of an anti-CCL4 antibody with MAT.Ang-1 resulted in a significant reduction in neutrophil recruitment. These data indicate a pro-inflammatory role for Ang-1 with respect to neutrophil recruitment.
Optimizing the thermoelectric performance of graphene nano-ribbons without degrading the electronic properties
Authors: Tran Van-Truong , Saint-Martin Jérôme , Dollfus Philippe , Volz Sebastian
Published: May 2017

The enhancement of thermoelectric figure of merit ZT requires to either increase the power factor or reduce the phonon conductance, or even both. In graphene, the high phonon thermal conductivity is the main factor limiting the thermoelectric conversion. The common strategy to enhance ZT is therefore to introduce phonon scatterers to suppress the phonon conductance while retaining high electrical conductance and Seebeck coefficient. Although thermoelectric performance is eventually enhanced, all studies based on this strategy show a significant reduction of the electrical conductance. In this study we demonstrate that appropriate sources of disorder, including isotopes and vacancies at lowest electron density positions, can be used as phonon scatterers to reduce the phonon conductance in graphene ribbons without degrading the electrical conductance, particularly in the low-energy region which is the most important range for device operation. By means of atomistic calculations we show that the natural electronic properties of graphene ribbons can be fully preserved while their thermoelectric efficiency is strongly enhanced. For ribbons of width M = 5 dimer lines, room-temperature ZT is enhanced from less than 0.26 to more than 2.5. This study is likely to set the milestones of a new generation of nano-devices with dual electronic/thermoelectric functionalities.
Callistemenonone A, a novel dearomatic dibenzofuran-type acylphloroglucinol with antimicrobial activity from Callistemon viminalis
Authors: Xiang Yu-Qing , Liu Hong-Xin , Zhao Li-Yun , Xu Zhi-Fang , Tan Hai-Bo , Qiu Sheng-Xiang
Published: May 2017

A new acylphloroglucinol with a novel architecture including an unprecedented dearomatic dibenzofuran core, named callistemenonone A (1), was isolated from the leaves of Callistemon viminalis (Myrtaceae). The structure was fully characterized on the basis of extensive spectroscopic analysis, including UV, HRESIMS, as well as 1D and 2D NMR spectral data (HSQC, HMBC, and ROESY). The deduced structure represents the first example of a natural dibenzofuran with two phenyl moieties coupling through tertiary hydroxy and ketal carbons. A plausible biogenetic pathway involving oxidative coupling and dearomatization as key steps is proposed to account for the biosynthesis of this novel class of dibenzofuran. Moreover, antimicrobial assays, in conjunction with the time-killing and biophysical studies, revealed that 1 exerted potent bactericidal activity against a panel of methicillin resistant pathogenic microbes with a unique mechanism.
PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production
Authors: Serrero Manutea , Planès Rémi , Bahraoui Elmostafa
Published: May 2017

HIV-1 Tat protein induces the production of CXCL8 chemokine in a TLR4/MD2 and PKC dependent manner. The objective of this study was to understand whether these two pathways were distinct or constituted a single common pathway, and to determine the nature of the PKC isoforms involved and their interrelation with the activation of NF-κB and CXCL8 gene product expression. Here, we show that Tat-induced CXCL8 production is essentially dependent on the activation of PKC delta isoform, as shown a) by the capacity of PKC delta dominant negative (DN), and Rottlerin, a selective PKC delta pharmacological inhibitor, to inhibit Tat-induced CXCL8 production and b) by the ability of the constitutively active (CAT) isoform of PKC delta to induce CXCL8 production in a HEK cell line in the absence of Tat stimulation. The finding that comparable amounts of CXCL8 were produced following stimulation with either Tat protein, PKC-delta CAT transfection, or both, argue for the implication of one common pathway where PKC delta is activated downstream of TLR4 recruitment and leads to the activation of NF-κB. Altogether, our results underline the crucial role of PKC delta isoform in activating gene expression of CXCL8, a cytokine largely implicated in the physiopathology of HIV-1 infection.
Sensorimotor adaptation as a behavioural biomarker of early spinocerebellar ataxia type 6
Authors: Panouillères Muriel T. N. , Joundi Raed A. , Benitez-Rivero Sonia , Cheeran Binith , Butler Christopher R. , Németh Andrea H. , Miall R. Chris , Jenkinson Ned
Published: May 2017

Early detection of the behavioural deficits of neurodegenerative diseases may help to describe the pathogenesis of such diseases and establish important biomarkers of disease progression. The aim of this study was to identify how sensorimotor adaptation of the upper limb, a cerebellar-dependent process restoring movement accuracy after introduction of a perturbation, is affected at the pre-clinical and clinical stages of spinocerebellar ataxia type 6 (SCA6), an inherited neurodegenerative disease. We demonstrate that initial adaptation to the perturbation was significantly impaired in the eighteen individuals with clinical motor symptoms but mostly preserved in the five pre-clinical individuals. Moreover, the amount of error reduction correlated with the clinical symptoms, with the most symptomatic patients adapting the least. Finally both pre-clinical and clinical individuals showed significantly reduced de-adaptation performance after the perturbation was removed in comparison to the control participants. Thus, in this large study of motor features in SCA6, we provide novel evidence for the existence of subclinical motor dysfunction at a pre-clinical stage of SCA6. Our findings show that testing sensorimotor de-adaptation could provide a potential predictor of future motor deficits in SCA6.
Strontium-loaded titania nanotube arrays repress osteoclast differentiation through multiple signalling pathways: In vitro and in vivo studies
Authors: Mi Baoguo , Xiong Wei , Xu Na , Guan Hanfeng , Fang Zhong , Liao Hui , Zhang Yong , Gao Biao , Xiao Xiang , Fu Jijiang , Li Feng
Published: May 2017

The loosening of implants is an important clinical issue, particularly for patients with osteoporosis. In these patients, an implant should preferably both promote osteoblast differentiation and repress osteoclastic resorption. In the present study, we fabricated coatings containing TiO2 nanotubes (NTs) incorporated with strontium (Sr) on titanium (Ti) surfaces through hydrothermal treatment. The amount of loaded Sr was controlled by hydrothermally treating the samples in a Sr(OH)2 solution for 1 and 3 h (samples NT-Sr1h and NT-Sr3h, respectively) and found that both types of NT-Sr samples inhibited osteoclast differentiation by reducing the expression of osteoclast marker genes. Additionally, this inhibitory effect was mainly attributed to suppression of RANKL-induced activation of nuclear factor-κB (NF-κB). Moreover, NT-Sr also inhibited the Akt and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) signalling pathways. Interestingly, we also found that NT-Sr promoted RANKL-induced extracellular signal-regulated kinase (ERK) phosphorylation. Using ovariectomised rats as a model, we observed that NT-Sr prevented bone loss in vivo. In conclusion, our findings demonstrate that NT-Sr might effectively inhibit osteoclast differentiation by repressing the NF-κB and Akt/NFATc1 pathways and by negatively regulating the ERK pathway in vitro and in vivo.
Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
Authors: Chen Chun-Yu , Wang Pin-Yi , Hutzen Brian , Sprague Les , Swain Hayley M. , Love Julia K. , Stanek Joseph R. , Boon Louis , Conner Joe , Cripe Timothy P.
Published: May 2017

Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer. In syngeneic murine rhabdomyosarcoma models, we found that M3-9-M (MHC I high) but not 76-9 (MHC I low) tumors respond to oncolytic herpes simplex virus-1 (oHSV-1) and PD-1 blockade combination therapy. In addition, the therapeutic outcomes in M3-9-M tumor models correlated with the increased incidence of CD4+ and CD8+ T cells but not with the CD4+CD25+Foxp3+ regulatory T cell populations in the tumor. Overall, our data suggest the combination of PD-1 blockade and oHSV-1 may be an effective treatment strategy for childhood soft tissue sarcoma.
Characterization of the Adult Head Transcriptome and Identification of Migration and Olfaction Genes in the Oriental Armyworm Mythimna separate
Authors: Bian Hai-Xu , Ma Hong-Fang , Zheng Xi-Xi , Peng Ming-Hui , Li Yu-Ping , Su Jun-Fang , Wang Huan , Li Qun , Xia Run-Xi , Liu Yan-Qun , Jiang Xing-Fu
Published: May 2017

The oriental armywormMythimna separateis an economically important insect with a wide distribution and strong migratory activity. However, knowledge about the molecular mechanisms regulating the physiological and behavioural responses of the oriental armyworm is scarce. In the present study, we took a transcriptomic approach to characterize the gene network in the adult head ofM.separate. The sequencing andde novoassembly yielded 63,499 transcripts, which were further assembled into 46,459 unigenes with an N50 of 1,153 bp. In the head transcriptome data, unigenes involved in the ‘signal transduction mechanism’ are the most abundant. In total, 937 signal transduction unigenes were assigned to 22 signalling pathways. The circadian clock, melanin synthesis, and non-receptor protein of olfactory gene families were then identified, and phylogenetic analyses were performed with theseM.separategenes, the model insectBombyxmoriand other insects. Furthermore, 1,372 simple sequence repeats of 2–6 bp in unit length were identified. The transcriptome data represent a comprehensive molecular resource for the adult head ofM.separate, and these identified genes can be valid targets for further gene function research to address the molecular mechanisms regulating the migratory and olfaction genes of the oriental armyworm.
Coupling mechanism between wear and oxidation processes of 304 stainless steel in hydrogen peroxide environments
Authors: Dong Conglin , Yuan Chengqing , Bai Xiuqin , Li Jian , Qin Honglin , Yan Xinping
Published: May 2017

Stainless steel is widely used in strongly oxidizing hydrogen peroxide (H2O2) environments. It is crucial to study its wear behaviour and failure mode. The tribological properties and oxidation of 304 stainless steel were investigated using a MMW-1 tribo-tester with a three-electrode setup in H2O2 solutions with different concentrations. Corrosion current densities (CCDs), coefficients of frictions (COFs), wear mass losses, wear surface topographies, and metal oxide films were analysed and compared. The results show that the wear process and oxidation process interacted significantly with each other. Increasing the concentration of H2O2 or the oxidation time was useful to form a layer of integrated, homogeneous, compact and thick metal oxide film. The dense metal oxide films with higher mechanical strengths improved the wear process and also reduced the oxidation reaction. The wear process removed the metal oxide films to increase the oxidation reaction. Theoretical data is provided for the rational design and application of friction pairs in oxidation corrosion conditions.
Prognostic importance of circulating epidermal growth factor-like domain 7 in patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab
Authors: Hansen Torben Frøstrup , Andersen Rikke Fredslund , Olsen Dorte Aalund , Sørensen Flemming Brandt , Jakobsen Anders
Published: May 2017

High tumor expression of epidermal growth factor-like domain 7 (EGFL7) has been associated with a poor prognosis in colorectal cancer. The aim of the current study was to investigate the possible prognostic impact of circulating EGFL7 (cir-EGFL7), combined with single nucleotide polymorphism (SNP) analyses, in patients with metastatic colorectal cancer (mCRC) treated with first line chemotherapy and bevacizumab. A total of 88 patients were included. Serum was collected prior to treatment initiation, at first evaluation after 3 weeks, and at progression. Cir-EGFL7 was analysed by the enzyme-linked immunosorbent assay (ELISA) technique. The SNPs were analysed by real-time qPCR based on DNA from whole blood. Endpoints were response rate (RR), progression free survival (PFS), and overall survival (OS). Cir-EGFL7 decreases after administration of chemotherapy plus bevacizumab. Baseline levels of cir-EGFL7 were significantly related to PFS and OS, p = 0.0431 and p = 0.0017, respectively, with increasing cir-EGFL7 levels associated with a worse prognosis. Circulating EGFL7 was not associated with RR. The SNP analyses revealed a significant relationship between rs1051851 and OS, p = 0.030. This study demonstrates that cir-EGFL7 changes during treatment with chemotherapy plus bevacizumab and that baseline levels and genetic variations may influence the overall prognosis of patients with mCRC. The findings call for further validation.
ABCC2 is associated with Bacillus thuringiensis Cry1Ac toxin oligomerization and membrane insertion in diamondback moth
Authors: Ocelotl Josue , Sánchez Jorge , Gómez Isabel , Tabashnik Bruce E. , Bravo Alejandra , Soberón Mario
Published: May 2017

Cry1A insecticidal toxins bind sequentially to different larval gut proteins facilitating oligomerization, membrane insertion and pore formation. Cry1Ac interaction with cadherin triggers oligomerization. However, a mutation in an ABC transporter gene (ABCC2) is linked to Cry1Ac resistance in Plutella xylostella. Cry1AcMod, engineered to lack helix α-1, was able to form oligomers without cadherinbinding and effectively countered Cry1Ac resistance linked to ABCC2. Here we analyzed Cry1Ac and Cry1AcMod binding and oligomerization by western blots using brush border membrane vesicles (BBMV) from a strain of P. xylostella susceptible to Cry1Ac (Geneva 88) and a strain with resistance to Cry1Ac (NO-QAGE) linked to an ABCC2 mutation. Resistance correlated with lack of specific binding and reduced oligomerization of Cry1Ac in BBMV from NO-QAGE. In contrast, Cry1AcMod bound specifically and still formed oligomers in BBMV from both strains. We compared association of pre-formed Cry1Ac oligomer, obtained by incubating Cry1Ac toxin with a Manduca sexta cadherin fragment, with BBMV from both strains. Our results show that pre-formed oligomers associate more efficiently with BBMV from Geneva 88 than with BBMV from NO-QAGE, indicating that the ABCC2 mutation also affects the association of Cry1Ac oligomer with the membrane. These data indicate, for the first time, that ABCC2 facilitates Cry1Ac oligomerization and oligomer membrane insertion in P. xylostella.
Involvement of the bed nucleus of the stria terminalis in L-Dopa induced dyskinesia
Authors: Bastide Matthieu F. , Glangetas Christelle , Doudnikoff Evelyne , Li Qin , Bourdenx Mathieu , Fernagut Pierre-Olivier , Dumont Éric C. , Georges François , Bézard Erwan
Published: May 2017

A whole brain immediate early gene mapping highlighted the dorsolateral bed nucleus of the stria terminalis (dlBST) as a structure putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID), the debilitating side-effects of chronic dopamine replacement therapy in Parkinson’s disease (PD). dlBST indeed displayed an overexpression of ∆FosB, ARC, Zif268 and FRA2 only in dyskinetic rats. We thus hypothesized that dlBST could play a role in LID hyperkinetic manifestations. To assess the causal role of the dlBST in LID, we used Daun02 inactivation to selectively inhibit the electrical activity of dlBST ΔFosB-expressing neurons. Daun02 is a prodrug converted into Daunorubicin by ß-galactosidase. Then, the newly synthesized Daunorubicin is an inhibitor of neuronal excitability. Therefore, following induction of abnormal involuntary movements (AIMs), 6-OHDA rats were injected with Daun02 in the dlBST previously expressing ß-galactosidase under control of the FosB/ΔFosB promoter. Three days after Daun02 administration, the rats were tested daily with L-Dopa to assess LID. Pharmacogenetic inactivation of ∆FosB-expressing neuron electrophysiological activity significantly reduced AIM severity. The present study highlights the role of dlBST in the rodent analog of LID, offering a new target to investigate LID pathophysiology.
Simvastatin and Bezafibrate ameliorate Emotional disorder Induced by High fat diet in C57BL/6 mice
Authors: Wang Hui , Zhou Jia , Liu Qiong Zhen , Wang Lu Lu , Shang Jing
Published: May 2017

High fat diet (HFD)-induced metabolic disorders may lead to emotional disorders. This study aimed to explore the effect of simvastatin (SMV) and bezafibrate (BZ) on improving HFD-induced emotional changes, and tried to identify their different mechanisms. The intraperitoneal glucose tolerance test (IPGTT) was used to evaluate glucose control ability; and behavior tests including open field tests (OFT), forced swimming tests (FST), tail suspension tests (TST) and sucrose preference (SPT), were then performed to evaluate emotional changes. Serum samples were collected for the LC-MS based metabolomics analysis to explore the emotional-related differential compounds; we then evaluated the effect of the drugs. The abnormal serum metabolic profiling and emotional changes caused by HFD in mice was alleviated by SMV treatment, whereas BZ only affected the emotional disorder. The improvement of cannabinoid analogues and then produced influences on the endocannabinoid system, which may be a potential mechanism SMV action. BZ promoted tryptophan-serotonin pathway and inhibited tryptophan-kynurenine pathway, which may be its mechanism of action. Here, we proposed a shed light on the biological mechanisms underlying the observed effects, and identified an important drug candidate for the treatment of emotional disorders induced by HFD.