bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent class regression models for simultaneously estimating test accuracy, true prevalence and risk factors for Brucella abortus
Authors: CAMPE A. , ABERNETHY D. , MENZIES F. , GREINER M.
Published: February 2016

In 2003/2004 a field trial was conducted in Northern Ireland to assess the diagnostic accuracy of six serological tests for bovine brucellosis caused by Brucella abortus. Whereas between-test comparisons have been used to calculate test performances so far, the present study used a latent class approach to estimate diagnostic test accuracy parameters in the absence of a gold standard for these six tests simultaneously and to estimate the true prevalence, while accounting for clustering in the study population and risk factors for true prevalence. Results obtained in this study with regard to prevalence, sensitivity and specificity were largely in accordance with previous findings. Screening tests (SAT and EDTA) appeared to be the most sensitive; however, at low prevalences the EDTA and CFT showed the highest positive predictive values of all investigated tests. The specificities and negative predictive values of all diagnostic tests were found to be very high. Differences of prevalence between three groups of the study population with different risk of exposure could be attributed to the mode of sampling indicating that a more risk-based sampling will result in a higher prevalence than a cross-sectional sampling mode. Age, dairy status and history of abortion were shown to influence the prediction of the latent true infection status.
Non-heat-treated frozen raspberries the most likely vehicle of a norovirus outbreak in Oslo, Norway, November 2013
Authors: EINÖDER-MORENO M. , LANGE H. , GREPP M. , OSBORG E. , VAINIO K. , VOLD L.
Published: February 2016

In November 2013, the Norwegian Institute of Public Health was notified of a gastroenteritis outbreak following two meetings held at a conference centre. Identical food and beverages were served during the meetings. We investigated in order to identify the vehicle of infection and implement control measures. Meeting participants completed an online questionnaire on consumption of foods and beverages. We asked symptomatic participants to provide a stool sample. We defined a case as diarrhoea and/or vomiting in a participant who became ill within 3 days after the meeting. We calculated attack rates (AR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI) using binomial regression. We conducted environmental investigations. Overall, 147/168 (88%) participants responded, of which 74 (50%) met the case definition. All five stool samples provided were norovirus positive. No kitchen staff reported being sick. Risk of illness was higher in those who consumed raspberry mousse (aRR 3·4, 95% CI 1·4–8·2) and sliced fresh fruit (aRR 1·9, 95% CI 1·3–2·8). Seventy cases (95%) ate raspberry mousse. Frozen raspberries used for the mousse were imported and not heat-treated before consumption. Non-heat-treated frozen raspberries were the most likely outbreak vehicle. Contamination by a food handler could not be excluded. We recommend heat-treatment of imported frozen berries before consumption.
Patterns of tourism in the Antarctic Peninsula region: a 20-year analysis
Authors: Bender Nicole A. , Crosbie Kim , Lynch Heather J.
Published: February 2016

We extend a previous analysis of Antarctic tour ship vessel traffic to include 20 years of commercial cruise activity (1993/94–2012/13) using recently digitized historical records and new data on vessel landings since 2008/09. Using tourism statistics from 1989/90–2013/14, we also examine trends in passenger numbers, landings and the nationalities of passengers travelling to the Antarctic Peninsula region. This study represents the most comprehensive long-term perspective on how tour ship activity has changed spatially and temporally over a period in which visitation has grown ten-fold. Passenger landings and marine traffic are highly concentrated at a few specific locations, particularly along the Peninsula’s south-western coast. Antarctic tourism activity is closely correlated with measures of economic activity in those countries contributing the largest numbers of visitors to the region. The nationalities of Antarctic tourists have shifted over the years, particularly with respect to an increasing number of visitors from China. Since emerging markets for Antarctic travel are probably far from saturated, interest in travelling to Antarctica will probably continue to grow. Understanding visitation patterns will focus efforts to monitor potential anthropogenic impacts and inform management decisions regarding activities in and around the Antarctic region.
Analysis of 2 + 1 diffusive–dispersive PDE arising in river braiding
Authors: TANVEER SALEH , TSIKKOU CHARIS
Published: February 2016

We present local existence and uniqueness results for the following 2 + 1 diffusive–dispersive equation due to P. Hall arising in modelling of river braiding:

$$\begin{equation*}
u_{yyt} - \gamma u_{xxx} -\alpha u_{yyyy} - \beta u_{yy} + \left ( u^2 \right )_{xyy} = 0 \end{equation*}$$

for (x,y) ∈ [0, 2π] × [0, π], t > 0, with boundary condition uy=0=uyyy at y=0 and y=π and 2π periodicity in x, using a contraction mapping argument in a Bourgain-type space Ts,b. We also show that the energy ∥u(·, ·, t)∥2L2 and cumulative dissipation ∫0t∥uy (·, ·, s)∥L22dt are globally controlled in time t.
BUCHANAN’S NON-COERCIVE ECONOMICS FOR SELF-INTERESTED INDIVIDUALS: ETHICS, SMALL GROUPS, AND THE SOCIAL CONTRACT
Authors: Marciano Alain
Published: February 2016

Market failures, which are usually viewed as a consequence of self-interest, are also supposed to be a major justification for coercive state interventions. This was the view of, among others, Richard Musgrave and Paul Samuelson, but not of James Buchanan. The latter certainly admitted that individuals are self-interested, that markets fail to allocate resources efficiently, but did not believe in the need for coercion. In this paper, we show that, to Buchanan, coercion can be unnecessary if certain post-constitutional conditions are satisfied. We show that he believed that self-interested individuals voluntarily adopt pro-social behavior in small groups. Small groups or small numbers represent a post-constitutional alternative to the veil of ignorance.
ADAM SMITH’S LAST TEACHINGS: DIALECTICAL WISDOM
Authors: Garbo Lorenzo
Published: February 2016

This paper focuses on the teachings and admonitions regarding wisdom found in the sixth edition of Adam Smith’s Theory of Moral Sentiments (TMS). Following a mind-path marked by the seminal contributions of Glenn Morrow (1923), Donald Winch (1978), and Laurence Dickey (1986), the paper offers an interpretation of the higher moral standard (superior prudence) introduced by Smith in the last edition of TMS, as his response to the socio-economic and cultural changes that took place in Great Britain in the second half of the eighteenth century. Between the first and last editions of TMS the taste for luxury and conspicuous consumption became widespread and contagious both geographically and across ranks. Prudence and other-approbation, sufficient gatekeepers of moral conduct and character in the previous editions of TMS, became progressively less effective in keeping society away from moral deception and in regulating reputation and the distinction of ranks. The paper examines the introduction of superior prudence in the last edition of TMS as Smith’s vision of a dialectical process between external and internal approbation that is capable of transforming individual dependence on social praise into a dialogue between materialistic and moral concerns, which would lead to a progressively wiser, although conflictual, existence.
Validation of self-reported figural drawing scales against anthropometric measurements in adults
Authors: Dratva Julia , Bertelsen Randi , Janson Christer , Johannessen Ane , Benediktsdóttir Bryndis , Bråbäck Lennart , Dharmage Shyamali C , Forsberg Bertil , Gislason Thorarinn , Jarvis Debbie , Jogi Rain , Lindberg Eva , Norback Dan , Omenaas Ernst , Skorge Trude D , Sigsgaard Torben , Toren Kjell , Waatevik Marie , Wieslander Gundula , Schlünssen Vivi , Svanes Cecilie , Real Francisco Gomez
Published: February 2016

Objective

The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys.

Design

Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model.

Setting

Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since.

Subjects

Individuals aged 38–66 years with complete data for BMI (n 1580) and waist circumference (n 1017).

Results

Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25·0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI.

Conclusions

Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible.
Determination of Electron Optical Properties for Aperture Zoom Lenses Using an Artificial Neural Network Method
Authors: Isik Nimet
Published: February 2016

Multi-element electrostatic aperture lens systems are widely used to control electron or charged particle beams in many scientific instruments. By means of applied voltages, these lens systems can be operated for different purposes. In this context, numerous methods have been performed to calculate focal properties of these lenses. In this study, an artificial neural network (ANN) classification method is utilized to determine the focused/unfocused charged particle beam in the image point as a function of lens voltages for multi-element electrostatic aperture lenses. A data set for training and testing of ANN is taken from the SIMION 8.1 simulation program, which is a well known and proven accuracy program in charged particle optics. Mean squared error results of this study indicate that the ANN classification method provides notable performance characteristics for electrostatic aperture zoom lenses.
Evidence for quorum sensing and differential metabolite production by a marine bacterium in response to DMSP
Authors: Johnson Winifred M , Kido Soule Melissa C , Kujawinski Elizabeth B
Published: February 2016

Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l-homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter.
Arbitrary cross-section SEM-cathodoluminescence imaging of growth sectors and local carrier concentrations within micro-sampled semiconductor nanorods
Authors: Watanabe Kentaro , Nagata Takahiro , Oh Seungjun , Wakayama Yutaka , Sekiguchi Takashi , Volk János , Nakamura Yoshiaki
Published: February 2016

Future one-dimensional electronics require single-crystalline semiconductor free-standing nanorods grown with uniform electrical properties. However, this is currently unrealistic as each crystallographic plane of a nanorod grows at unique incorporation rates of environmental dopants, which forms axial and lateral growth sectors with different carrier concentrations. Here we propose a series of techniques that micro-sample a free-standing nanorod of interest, fabricate its arbitrary cross-sections by controlling focused ion beam incidence orientation, and visualize its internal carrier concentration map. ZnO nanorods are grown by selective area homoepitaxy in precursor aqueous solution, each of which has a (0001):+c top-plane and six {1–100}:m side-planes. Near-band-edge cathodoluminescence nanospectroscopy evaluates carrier concentration map within a nanorod at high spatial resolution (60 nm) and high sensitivity. It also visualizes +c and m growth sectors at arbitrary nanorod cross-section and history of local transient growth events within each growth sector. Our technique paves the way for well-defined bottom-up nanoelectronics.
Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain
Authors: Freyberg Zachary , Sonders Mark S. , Aguilar Jenny I. , Hiranita Takato , Karam Caline S. , Flores Jorge , Pizzo Andrea B. , Zhang Yuchao , Farino Zachary J. , Chen Audrey , Martin Ciara A. , Kopajtic Theresa A. , Fei Hao , Hu Gang , Lin Yi-Ying , Mosharov Eugene V. , McCabe Brian D. , Freyberg Robin , Wimalasena Kandatege , Hsin Ling-Wei , Sames Dalibor , Krantz David E. , Katz Jonathan L. , Sulzer David , Javitch Jonathan A.
Published: February 2016

Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT’s role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H+ antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.
Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway
Authors: Park Sung Ryeol , Tripathi Ashootosh , Wu Jianfeng , Schultz Pamela J. , Yim Isaiah , McQuade Thomas J. , Yu Fengan , Arevang Carl-Johan , Mensah Abraham Y. , Tamayo-Castillo Giselle , Xi Chuanwu , Sherman David H.
Published: February 2016

Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 μM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 μM).
Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals
Authors: Montagner Alexandra , Korecka Agata , Polizzi Arnaud , Lippi Yannick , Blum Yuna , Canlet Cécile , Tremblay-Franco Marie , Gautier-Stein Amandine , Burcelin Rémy , Yen Yi-Chun , Je Hyunsoo Shawn , Al-Asmakh Maha , Mithieux Gilles , Arulampalam Velmurugesan , Lagarrigue Sandrine , Guillou Hervé , Pettersson Sven , Wahli Walter
Published: February 2016

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose and xenobiotic metabolism, protein turnover and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function.
Enhancing the energy density of safer Li-ion batteries by combining high-voltage lithium cobalt fluorophosphate cathodes and nanostructured titania anodes
Authors: Ortiz Gregorio F. , López María C. , Li Yixiao , McDonald Matthew J. , Cabello Marta , Tirado José L. , Yang Yong
Published: February 2016

Recently, Li-ion batteries have been heavily scrutinized because of the apparent incompatibility between safety and high energy density. This work report a high voltage full battery made with TiO2/Li3PO4/Li2CoPO4F. The Li2CoPO4F cathode and TiO2 anode materials are synthesized by a sol–gel and anodization methods, respectively. X-ray diffraction (XRD) analysis confirmed that Li2CoPO4F is well-crystallized in orthorhombic crystal structure with Pnma space group. The Li3PO4-coated anode was successfully deposited as shown by the (011) lattice fringes of anatase TiO2 and (200) of γ-Li3PO4, as detected by HRTEM. The charge profile of Li2CoPO4F versus lithium shows a plateau at 5.0 V, revealing its importance as potentially high-voltage cathode and could perfectly fit with the plateau of anatase anode (1.8–1.9 V). The full cell made with TiO2/Li3PO4/Li2CoPO4F delivered an initial reversible capacity of 150 mA h g−1 at C rate with good cyclic performance at an average potential of 3.1–3.2 V. Thus, the full cell provides an energy density of 472 W h kg−1. This full battery behaves better than TiO2/Li2CoPO4F. The introduction of Li3PO4 as buffer layer is expected to help the cyclability of the electrodes as it allows a rapid Li-ion transport.
IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity
Authors: Avnir Yuval , Watson Corey T. , Glanville Jacob , Peterson Eric C. , Tallarico Aimee S. , Bennett Andrew S. , Qin Kun , Fu Ying , Huang Chiung-Yu , Beigel John H. , Breden Felix , Zhu Quan , Marasco Wayne A.
Published: February 2016

IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of “universal” influenza vaccine.
Remarkably enhanced thermal transport based on a flexible horizontally-aligned carbon nanotube array film
Authors: Qiu Lin , Wang Xiaotian , Su Guoping , Tang Dawei , Zheng Xinghua , Zhu Jie , Wang Zhiguo , Norris Pamela M. , Bradford Philip D. , Zhu Yuntian
Published: February 2016

It has been more than a decade since the thermal conductivity of vertically aligned carbon nanotube (VACNT) arrays was reported possible to exceed that of the best thermal greases or phase change materials by an order of magnitude. Despite tremendous prospects as a thermal interface material (TIM), results were discouraging for practical applications. The primary reason is the large thermal contact resistance between the CNT tips and the heat sink. Here we report a simultaneous sevenfold increase in in-plane thermal conductivity and a fourfold reduction in the thermal contact resistance at the flexible CNT-SiO2 coated heat sink interface by coupling the CNTs with orderly physical overlapping along the horizontal direction through an engineering approach (shear pressing). The removal of empty space rapidly increases the density of transport channels and the replacement of the fine CNT tips with their cylindrical surface insures intimate contact at CNT-SiO2 interface. Our results suggest horizontally aligned CNT arrays exhibit remarkably enhanced in-plane thermal conductivity and reduced out-of-plane thermal conductivity and thermal contact resistance. This novel structure makes CNT film promising for applications in chip-level heat dissipation. Besides TIM, it also provides for a solution to anisotropic heat spreader which is significant for eliminating hot spots.
Quantitative secondary electron imaging for work function extraction at atomic level and layer identification of graphene
Authors: Zhou Yangbo , Fox Daniel S , Maguire Pierce , O’Connell Robert , Masters Robert , Rodenburg Cornelia , Wu Hanchun , Dapor Maurizio , Chen Ying , Zhang Hongzhou
Published: February 2016

Two-dimensional (2D) materials usually have a layer-dependent work function, which require fast and accurate detection for the evaluation of their device performance. A detection technique with high throughput and high spatial resolution has not yet been explored. Using a scanning electron microscope, we have developed and implemented a quantitative analytical technique which allows effective extraction of the work function of graphene. This technique uses the secondary electron contrast and has nanometre-resolved layer information. The measurement of few-layer graphene flakes shows the variation of work function between graphene layers with a precision of less than 10 meV. It is expected that this technique will prove extremely useful for researchers in a broad range of fields due to its revolutionary throughput and accuracy.
A novel role for Crp in controlling magnetosome biosynthesis in Magnetospirillum gryphiswaldense MSR-1
Authors: Wen Tong , Guo Fangfang , Zhang Yunpeng , Tian Jiesheng , Li Ying , Li Jilun , Jiang Wei
Published: February 2016

Magnetotactic bacteria (MTB) are specialized microorganisms that synthesize intracellular magnetite particles called magnetosomes. Although many studies have focused on the mechanism of magnetosome synthesis, it remains unclear how these structures are formed. Recent reports have suggested that magnetosome formation is energy dependent. To investigate the relationship between magnetosome formation and energy metabolism, a global regulator, named Crp, which mainly controls energy and carbon metabolism in most microorganisms, was genetically disrupted in Magnetospirillum gryphiswaldense MSR-1. Compared with the wild-type or complemented strains, the growth, ferromagnetism and intracellular iron content of crp-deficient mutant cells were dramatically decreased. Transmission electron microscopy (TEM) showed that magnetosome synthesis was strongly impaired by the disruption of crp. Further gene expression profile analysis showed that the disruption of crp not only influenced genes related to energy and carbon metabolism, but a series of crucial magnetosome island (MAI) genes were also down regulated. These results indicate that Crp is essential for magnetosome formation in MSR-1. This is the first time to demonstrate that Crp plays an important role in controlling magnetosome biomineralization and provides reliable expression profile data that elucidate the mechanism of Crp regulation of magnetosome formation in MSR-1.
Effect of TGF-β1 on the Migration and Recruitment of Mesenchymal Stem Cells after Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14
Authors: Zhao Wei , Wang Chengyan , Liu Ruixue , Wei Cuilei , Duan Juncang , Liu Kejian , Li Shugang , Zou Hong , Zhao Jin , Wang Lianghai , Qi Yan , Liang Weihua , Jiang Jinfang , Zhang Wenjie , Pang Lijuan , Li Feng
Published: February 2016

Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-β1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-β1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-β1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-β1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29 and Sca1+CD29+CD11b/c−CD45−. Intimal hyperplasia was reduced in SB- and rhTGF-β1-treated rats. The expression of TGF-β1, TGF-β1RI and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF-β1 administration decreased the expression of TGF-β1/Smad pathway proteins, except for TGF-β1RI. Nestin and CD29 expression and the number of Sca1+CD29+CD11b−CD45− cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-β1 administration. These results suggest that TGF-β1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling.
Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages
Authors: Shi Lei , Zhang Zhe , Su Bing
Published: February 2016

There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex-biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer’s disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders.
A single residue substitution accounts for the significant difference in thermostability between two isoforms of human cytosolic creatine kinase
Authors: Liu Huihui , Gao Yan-Song , Chen Xiang-Jun , Chen Zhe , Zhou Hai-Meng , Yan Yong-Bin , Gong Haipeng
Published: February 2016

Creatine kinase (CK) helps maintain homeostasis of intracellular ATP level by catalyzing the reversible phosphotransfer between ATP and phosphocreatine. In humans, there are two cytosolic CK isoforms, the muscle-type (M) and the brain-type (B), which frequently function as homodimers (hMMCK and hBBCK). Interestingly, these isoenzymes exhibit significantly different thermostabilities, despite high similarity in amino acid sequences and tertiary structures. In order to investigate the mechanism of this phenomenon, in this work, we first used domain swapping and site-directed mutagenesis to search for the key residues responsible for the isoenzyme-specific thermostability. Strikingly, the difference in thermostability was found to principally arise from one single residue substitution at position 36 (Pro in hBBCK vs. Leu in hMMCK). We then engaged the molecular dynamics simulations to study the molecular mechanism. The calculations imply that the P36L substitution introduces additional local interactions around residue 36 and thus further stabilizes the dimer interface through a complex interaction network, which rationalizes the observation that hMMCK is more resistant to thermal inactivation than hBBCK. We finally confirmed this molecular explanation through thermal inactivation assays on Asp36 mutants that were proposed to devastate the local interactions and thus the dimer associations in both isoenzymes.
FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome
Authors: Tian Ye , Zhang Wei , Zhao Shigang , Sun Yinhua , Bian Yuehong , Chen Tailai , Du Yanzhi , Zhang Jiangtao , Wang Zhao , Huang Tao , Peng Yingqian , Yang Ping , Zhao Han , Chen Zi-Jiang
Published: February 2016

Dyslipidemia is common in polycystic ovary syndrome (PCOS). This study was aimed to investigate whether fatty acid desaturase genes (FADS), a dyslipidemia-related gene cluster, are associated with PCOS. We scanned variations of FADS genes using our previous data of genome-wide association study (GWAS) for PCOS and selected rs174570 for further study. The case-control study was conducted in an independent cohort of 1918 PCOS cases and 1889 age-matched controls and family-based study was conducted in a set of 243 core family trios with PCOS probands. Minor allele frequency (allele T) of rs174570 was significantly lower in PCOS cases than that in age-matched controls (P = 2.17E-03, OR = 0.85), even after adjustment of BMI and age. PCOS subjects carrying CC genotype had higher testosterone level and similar lipid/glucose level compared with those carrying TT or TC genotype. In trios, transmission disequilibrium test (TDT) analysis revealed risk allele C of rs174570 was significantly over-transmitted (P = 2.00E-04). Decreased expression of FADS2 was detected in PCOS cases and expression quantitative trait loci (eQTL) analysis revealed the risk allele C dosage was correlated with the decline of FADS2 expression (P = 0.002). Our results demonstrate that FADS1-FADS2 are susceptibility genes for PCOS.
Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells
Authors: Taverna Elena , Mora-Bermúdez Felipe , Strzyz Paulina J. , Florio Marta , Icha Jaroslav , Haffner Christiane , Norden Caren , Wilsch-Bräuninger Michaela , Huttner Wieland B.
Published: February 2016

Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture and fundamental Golgi re-organization upon cell fate change.
Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms
Authors: Misaki Masaya , Suzuki Hideo , Savitz Jonathan , Drevets Wayne C. , Bodurka Jerzy
Published: February 2016

Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD.
Differential regulation of taurine biosynthesis in rainbow trout and Japanese flounder
Authors: Wang Xuan , He Gen , Mai Kangsen , Xu Wei , Zhou Huihui
Published: February 2016

Animals have varied taurine biosynthesis capability, which was determined by activities of key enzymes including cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD). However, whether CDO and CSD are differentially regulated across species remains unexplored. In the present study, we examined the regulations of CDO and CSD in rainbow trout and Japanese flounder, the two fish species with high and low taurine biosynthesis ability respectively. Our results showed that the expression of CDO was lower in rainbow trout but more responsive to cysteine stimulation compared to that in Japanese flounder. On the other hand, both the expression and catalytic efficiency (kcat) of CSD were higher in rainbow trout than those of Japanese flounder. A three-residue substrate recognition motif in rainbow trout CSD with sequence of F126/S146/Y148was identified to be responsible for highkcat, while that with sequence of F88/N108/F110in Japanese flounder led to lowkcat, as suggested by site-directed mutagenesis studies. In summary, our results determined new aspects of taurine biosynthesis regulation across species.
Application of a novel phosphinothricin N-acetyltransferase (RePAT) gene in developing glufosinate-resistant rice
Authors: Cui Ying , Liu Ziduo , Li Yue , Zhou Fei , Chen Hao , Lin Yongjun
Published: February 2016

Currently, only few glufosinate-resistant genes are available for commercial application. Thus, developing novel glufosinate-resistant genes with commercial feasibility is extremely important and urgent for agricultural production. In this study, we transferred a newly isolated RePAT gene into a japonica rice variety Zhonghua11, resulting in a large number of independent T0 transgenic plants, most of which grew normally under high-concentration glufosinate treatment. Four transgenic plants with one intact RePAT expression cassette integrated into the intergenic region were selected. Agronomic performances of their T2 progenies were investigated, and the results suggested that the expression of RePAT had no adverse effect on the agronomic performance. Definite glufosinate resistance of the selected transgenic plants was further confirmed to be related to the expression of RePAT by assay on the medium and qRT-PCR. The inheritance and expression of RePAT in two transgenic plants were confirmed to be stable. Finally, the two-year field assay of glufosinate resistance suggested that the agronomic performance of the transgenic plant (PAT11) was not affected by high dosage of glufosinate (5000 g/ha). Collectively, our study proves the high resistance of a novel gene RePAT to glufosinate and provides a glufosiante-resistant rice variety with agricultural application potential.
Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling
Authors: Liu Feng , Zhang Wen , Yang Fusheng , Feng Tingting , Zhou Meng , Yu Yuan , Yu Xiuping , Zhao Weiming , Yi Fan , Tang Wei , Lu Yi
Published: February 2016

This study aimed to determine the expression of progranulin (PGRN) in hepatocellular carcinoma (HCC) cells in response to interleukin 6 (IL-6), a non-cellular component of the tumor microenvironment and the molecular mechanism of PGRN oncogenic activity in hepatocarcinogenesis. Levels of IL-6 and PGRN were increased and positively correlated in HCC tissues. IL-6 dose- and time-dependently increased PGRN level in HCC cells. IL-6-driven PGRN expression was at least in part mediated by Erk/C/EBPβ signaling and reduced expression of PGRN impaired IL-6-stimulated proliferation, migration and invasion of HepG2 cells. PGRN activated mammalian target of rapamycin (mTOR) signaling, as evidenced by increased phosphorylation of p70S6K, 4E-BP1 and Akt-Ser473/FoxO1. Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL-6-mediated proliferation, migration and invasion of HCC cells in vitro. Persistent activation of mTOR signaling by knockdown of TSC2 restored PGRN-knockdown-attenuated pro-proliferation effects of IL-6 in HepG2 cells. In addition, rapamycin treatment in vivo in mice slowed tumor growth stimulated by recombinant human PGRN. Our findings provide a better understanding of the biological activities of the IL-6/PGRN/mTOR cascade in the carcinogenesis of HCC, which may suggest a novel target in the treatment of HCC.
An ultrasensitive label-free electrochemical immunosensor based on signal amplification strategy of multifunctional magnetic graphene loaded with cadmium ions
Authors: Li Faying , Li Yueyun , Dong Yunhui , Jiang Liping , Wang Ping , Liu Qing , Liu Hui , Wei Qin
Published: February 2016

Herein, a novel and ultrasensitive label-free electrochemical immunosensor was proposed for quantitative detection of human Immunoglobulin G (IgG). The amino functionalized magnetic graphenes nanocomposites (NH2 -GS-Fe3O4) were prepared to bond gold and silver core-shell nanoparticles (Au@Ag NPs) by constructing stable Au-N and Ag-N bond between Au@Ag NPs and -NH2. Subsequently, the Au@Ag/GS-Fe3O4 was applied to absorb cadmium ion (Cd2+) due to the large surface area, high conductivity and exceptional adsorption capability. The functional nanocomposites of gold and silver core-shell magnetic graphene loaded with cadmium ion (Au@Ag/GS-Fe3O4/Cd2+) can not only increase the electrocatalytic activity towards hydrogen peroxide (H2O2) but also improve the effective immobilization of antibodies because of synergistic effect presented in Au@Ag/GS-Fe3O4/Cd2+, which greatly extended the scope of detection. Under the optimal conditions, the proposed immunosensor was used for the detection of IgG with good linear relation in the range from 5 fg/mL to 50 ng/mL with a low detection limit of 2 fg/mL (S/N = 3). Furthermore, the proposed immunosensor showed high sensitivity, special selectivity and long-term stability, which had promising application in bioassay analysis.
Watch your step! A frustrated total internal reflection approach to forensic footwear imaging
Authors: Needham J. A. , Sharp J. S.
Published: February 2016

Forensic image retrieval and processing are vital tools in the fight against crime e.g. during fingerprint capture. However, despite recent advances in machine vision technology and image processing techniques (and contrary to the claims of popular fiction) forensic image retrieval is still widely being performed using outdated practices involving inkpads and paper. Ongoing changes in government policy, increasing crime rates and the reduction of forensic service budgets increasingly require that evidence be gathered and processed more rapidly and efficiently. A consequence of this is that new, low-cost imaging technologies are required to simultaneously increase the quality and throughput of the processing of evidence. This is particularly true in the burgeoning field of forensic footwear analysis, where images of shoe prints are being used to link individuals to crime scenes. Here we describe one such approach based upon frustrated total internal reflection imaging that can be used to acquire images of regions where shoes contact rigid surfaces.
Automaticity of Conceptual Magnitude
Authors: Gliksman Yarden , Itamar Shai , Leibovich Tali , Melman Yonatan , Henik Avishai
Published: February 2016

What is bigger, an elephant or a mouse? This question can be answered without seeing the two animals, since these objects elicit conceptual magnitude. How is an object’s conceptual magnitude processed? It was suggested that conceptual magnitude is automatically processed; namely, irrelevant conceptual magnitude can affect performance when comparing physical magnitudes. The current study further examined this question and aimed to expand the understanding of automaticity of conceptual magnitude. Two different objects were presented and participants were asked to decide which object was larger on the screen (physical magnitude) or in the real world (conceptual magnitude), in separate blocks. By creating congruent (the conceptually larger object was physically larger) and incongruent (the conceptually larger object was physically smaller) pairs of stimuli it was possible to examine the automatic processing of each magnitude. A significant congruity effect was found for both magnitudes. Furthermore, quartile analysis revealed that the congruity was affected similarly by processing time for both magnitudes. These results suggest that the processing of conceptual and physical magnitudes is automatic to the same extent. The results support recent theories suggested that different types of magnitude processing and representation share the same core system.
Appearance of β-lactam Resistance Genes in Agricultural Soils and Clinical Isolates over the 20th Century
Authors: Graham David W. , Knapp Charles W. , Christensen Bent T. , McCluskey Seánín , Dolfing Jan
Published: February 2016

Debate exists about whether agricultural versus medical antibiotic use drives increasing antibiotic resistance (AR) across nature. Both sectors have been inconsistent at antibiotic stewardship, but it is unclear which sector has most influenced acquired AR on broad scales. Using qPCR and soils archived since 1923 at Askov Experimental Station in Denmark, we quantified four broad-spectrum β-lactam AR genes (ARG; blaTEM, blaSHV, blaOXA and blaCTX-M) and class-1 integron genes (int1) in soils from manured (M) versus inorganic fertilised (IF) fields. “Total” β-lactam ARG levels were significantly higher in M versus IF in soils post-1940 (paired-t test; p < 0.001). However, dominant individual ARGs varied over time; blaTEM and blaSHV between 1963 and 1974, blaOXA slightly later and blaCTX-M since 1988. These dates roughly parallel first reporting of these genes in clinical isolates, suggesting ARGs in animal manure and humans are historically interconnected. Archive data further show when non-therapeutic antibiotic use was banned in Denmark, blaCTX-M levels declined in M soils, suggesting accumulated soil ARGs can be reduced by prudent antibiotic stewardship. Conversely, int1 levels have continued to increase in M soils since 1990, implying direct manure application to soils should be scrutinized as part of future stewardship programs.
(−)-Epigallocatechin-3-Gallate Enhances Hepatitis C Virus Double-Stranded RNA Intermediates-Triggered Innate Immune Responses in Hepatocytes
Authors: Wang Yizhong , Li Jieliang , Wang Xu , Peña Juliet C. , Li Kui , Zhang Ting , Ho Wenzhe
Published: February 2016

(−)-Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, has recently been identified as an inhibitor of hepatitis C virus (HCV) entry. Here, we examined whether EGCG can enhance hepatocyte-mediated intracellular innate immunity against HCV. HCV dsRNAs (Core, E1-P7, NS-3′NTR and NS5A) induced interferon-λ1 (IFN-λ1) expression in human hepatocytes. These HCV dsRNAs also induced the expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and several antiviral IFN-stimulated genes (ISGs) expression. Although EGCG treatment of hepatocytes alone had little effect on TLR3 and RIG-I signaling pathways, EGCG significantly enhanced HCV dsRNAs-induced the expression of IFN-λ1, TLR3, RIG-I and antiviral ISGs in hepatocytes. Furthermore, treatment of HCV-infected hepatocytes with EGCG and HCV dsRNAs inhibited viral replication. Given that EGCG has the ability to enhance HCV dsRNAs-induced intracellular antiviral innate immunity against HCV, suggesting the potential application of EGCG as a new anti-HCV agent for HCV therapy.