bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and biochemical basis for induced self-propagation of NLRC4
Authors: Hu Zehan , Zhou Qiang , Zhang Chenlu , Fan Shilong , Cheng Wei , Zhao Yue , Shao Feng , Wang Hong-Wei , Sui Sen-Fang , Chai Jijie
Published: October 2015

Inflammasomes take the wheel

Cells require microbial ligand binding to sense pathogens (see the Perspective by Liu and Xiao). Binding to the family of NOD-like receptors triggers the assembly of large protein signaling complexes called inflammasomes, leading infected cells to die and produce inflammatory mediators. Hu
et al.
and Zhang
et al.
use cryo–electron microscopy to uncover the structural and biochemical basis of two such receptors: NAIP2, which directly binds microbial ligands, and NLRC4, a protein functioning directly downstream. A self-propagating activation mechanism of downstream inflammasome signaling starts with one molecule of NAIP4 directly binding its microbial ligand. NAIP4 then catalyzes the activation of 10 to 12 NLRC4 molecules to form a wheel-like structure.

Science
, this issue p.
399
,
404
; see also p.
376
Draft Genome Sequence of Campylobacter fetus MMM01, Isolated from a Chronic Kidney Disease Patient with Sepsis
Authors: Rohit Anusha , Kumar Ballamoole Krishna , Deekshit Vijay Kumar , Rai Praveen , Kumar Ramanathan Vijay , Jayaprakash Jayapalan , Madhushankara Bhat , Karunasagar Iddya , Karunasagar Indrani
Published: October 2015

Campylobacter fetus
is a Gram-negative bacterium that has caused several cases of human and animal disease. Here, we report the draft genome sequence of
C. fetus
MMM01, isolated from the blood of a 60-year-old patient with type II diabetes and chronic kidney disease. The sequence has a total length of 1,740,393 bp and an average G+C content of 33.1%. The availability of the draft genome sequence of
C. fetus
MMM01 isolated from a case of chronic kidney disease will contribute to a better understanding of the pathophysiological mechanisms of this organism.
Complete Genome Sequence of Caulobacter crescentus Siphophage Sansa
Authors: Vara Leonardo , Kane Ashley A. , Cahill Jesse L. , Rasche Eric S. , Kuty Everett Gabriel F.
Published: October 2015

Caulobacter crescentus
is a Gram-negative dimorphic model organism used to study cell differentiation. Siphophage Sansa is a newly isolated siphophage with an icosahedral capsid that infects
C. crescentus
. Sansa shares no sequence similarity to other phages deposited in GenBank. Here, we describe its genome sequence and general features.
Draft Genome Sequence of an Anthracimycin Producer,
Streptomyces
sp. TP-A0875
Authors: Komaki Hisayuki , Ichikawa Natsuko , Hosoyama Akira , Fujita Nobuyuki , Harunari Enjuro , Igarashi Yasuhiro
Published: October 2015

Here, we report the draft genome sequence of an anthracimycin producer,
Streptomyces
sp. TP-A0875. The genome contains at least two type I polyketide synthase (PKS) gene clusters, two type II PKS gene clusters, and three nonribosomal peptide synthetase gene clusters. The gene cluster for anthracimycin biosynthesis was identified based on the PKS domain organization.
A case of digital hoarding
Authors: van Bennekom Martine J , Blom Rianne M , Vulink Nienke , Denys Damiaan
Published: October 2015

A 47-year-old man presented to our outpatient clinic, preoccupied with hoarding of digital pictures, which severely interfered with his daily functioning. He was formerly diagnosed with autism and hoarding of tactile objects. As of yet, digital hoarding has not been described in the literature. With this case report, we would like to introduce ‘digital hoarding’ as a new subtype of hoarding disorder. We conclude with differential diagnostic considerations and suggestions for treatment.
Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry
Authors: Manders Sofie H M , van de Laar Mart A F J , Rongen-van Dartel Sanne A A , Bos Reinhard , Visser Henk , Brus Herman L , Jansen Tim , Vonkeman Harald E , van Riel Piet L C M , Kievit Wietske
Published: October 2015

Objectives

To study the number of patients that taper or discontinue concomitant methotrexate (MTX) in daily practice in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor inhibitor (TNFi) and to analyse the effects of that adaption on disease activity and drug survival.

Methods

Data were collected from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Patients who started their first TNFi were included in the study. Treatment effectiveness after MTX tapering or discontinuation was analysed using Disease Activity Score of 28 joints (DAS28). Drug survival of the TNFi was analysed using the Cox proportional hazard model with a time-dependent covariate.

Results

In 458 patients (34%), MTX was tapered, 126 patients (10%) discontinued MTX and 747 patients (56%) continued MTX at the same dose. On average, DAS28 improved after tapering MTX (−0.40, −0.45) and after stopping MTX (−0.28, −0.12) at 6 and 12 months. In the taper group, 21% of the patients relapsed (DAS28 increase >0.6), and in the discontinuation group this was 21% and 24% at 6 and 12 months, respectively. Patients who taper and discontinue MTX have a similar DAS28 score over time as patients who continue MTX. Moreover, there was no influence of tapering or discontinuation of MTX on long-term drug survival of TNFi.

Conclusions

In daily practice, tapering or discontinuation of concomitant MTX in patients with RA treated with TNFi frequently occurs and it does not seem to influence the average DAS28 over time or the long-term TNFi drug survival. It appears that in daily clinical practice the correct patients are selected to taper or discontinue MTX.
Intercontinental distributions of species of Cortinarius, subgenus Phlegmacium, associated with Populus in western North America
Authors: Cripps Cathy L. , Liimatainen Kare , Niskanen Tuula , Dima Bálint , Bishop Richard F. , Ammirati Joseph F.
Published: October 2015

Three species of Cortinarius subg. Phlegmacium, Cortinarius argutus Fr. and Cortinarius hedyaromaticus C. Cripps & O.K. Mill. (section Arguti stat. nov.) and Cortinarius talus Fr. (section Multiformes), are compared from western North America and Europe. Phylogenetic analysis of the ITS region shows that C. argutus and C. hedyaromaticus are separate, closely related species with rooting stipes. Cortinarius talus is a pale species with a bulbous stipe and a sweet odor similar to that of C. hedyaromaticus; C. argutus lacks this sweet odor. All three species have intercontinental distributions and are associated with deciduous trees, primarily Populus tremuloides Michx., Populus tremula L., but also Salix spp. This study highlights the importance of the study of type specimens and molecular analysis to stabilize the application of established names.
Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism
Authors: Abbas Amr M. , Sakr Hussein F.
Published: October 2015

Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-α, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals.
Wildlife research and management methods in the 21st century: Where do unmanned aircraft fit in?
Authors: Chabot Dominique , Bird David M.
Published: October 2015

Since the turn of the century, emerging unmanned aircraft systems (UAS) have found increasingly diverse applications in wildlife science as convenient, very high-resolution remote sensing devices. Achieved or conceptualized applications include optical surveying and observation of animals, autonomous wildlife telemetry tracking, and habitat research and monitoring. As the technology continues to progress and interest from the wildlife science community grows, there may yet be much untapped potential for UAS to contribute to the discipline. We present a review of the published primary literature on the application of UAS in wildlife science and related fields. This is followed by a systematic review of the broader wildlife science literature published since the turn of the century to assess where UAS are likely to make important contributions going forward based on the trends that have emerged thus far. UAS, in particular small lightweight models, are generally well suited for collecting data at an intermediate spatial scale between what is easily coverable on the ground and what is economically coverable with conventional aircraft. They are particularly useful for monitoring wildlife and habitats in places that are difficult to access or navigate from the ground, as well as approaching sensitive or aggressive species.
An Efficient yet Effective Random Partitioning and Feature Weighting Approach for Transfer Learning
Authors: Tahmoresnezhad Jafar , Hashemi Sattar
Published: October 2015

One of the serious challenges in machine learning and pattern recognition is to transfer knowledge from related but different domains to a new unlabeled domain. Feature selection with maximum mean discrepancy (f-MMD) is a novel and effective approach to transfer knowledge from source domain (training set) into target domain (test set) where training and test sets are drawn from different distributions. However, f-MMD has serious challenges in facing datasets with large number of samples and features. Moreover, f-MMD ignores the feature-label relation in finding the reduced representation of dataset. In this paper, we exploit jointly transfer learning and class discrimination to cope with domain shift problem on which the distribution difference is considerably large. We therefore put forward a novel transfer learning and class discrimination approach, referred to as RandOm k-samplesets feature Weighting Approach (ROWA). Specifically, ROWA reduces the distribution difference across domains in an unsupervised manner where no label is available in the test set. Moreover, ROWA exploits feature-label relation to separate various classes alongside the domain transfer, and augments the relation of selected features and source domain labels. In this work, we employ disjoint/overlapping small-sized samplesets to iteratively converge to final solution. Employment of local sets along with a novel optimization problem constructs a robust and effective reduced representation for adaptation across domains. Extensive experiments on real and synthetic datasets verify that ROWA can significantly outperform state-of-the-art transfer learning approaches.
Design of Digital Channelizer Based on Source Number Estimation
Authors: Hu Junpeng , Huang Zhiping , Liu Chunwu , Su Shaojing , Zhou Jing
Published: October 2015

Digital channelizer is used to separate the sub-band signals contained within a wideband intermediate frequency (IF) received signal. This paper presents a structure of digital channelizer which is built upon estimation of the sub-band signal number. The proposed structure is designed by employing nonuniform filter banks (NUFBs), which are implemented by merging the adjacent sub-branches of the perfect reconstruction (PR) cosine modulated filter banks (CMFBs). Using source number estimation algorithm, the estimated value of sub-band number can be obtained. By energy detection, the energy characteristic of the analysis filter banks (AFBs) can be acquired and another value of sub-band number is calculated. Comparing the estimated value and the calculated one, we can evaluate whether the design of the AFB is suitable for the received signal. The structure of digital channelizer proposed by this paper provides a potential way to channelize the unknown signal and suggests a solution for the dynamic channelizaiton. A design example is also presented to demonstrate the feasibility and simplicity of this method.
Electron and Muon production cross-sections in quasielastic ν(ν̄)-Nucleus scattering for Eν < 1GeV
Authors: Akbar F. , Alam M. Rafi , Athar M. Sajjad , Chauhan S. , Singh S. K. , Zaidi F.
Published: October 2015

In this paper, we have studied (anti)neutrino induced charged current quasielastic (CCQE) scattering from some nuclear targets in the energy region of [Formula: see text]. Our aim is to confront electron and muon production cross-sections relevant for [Formula: see text] or [Formula: see text] oscillation experiments. The effects due to lepton mass and its kinematic implications, radiative corrections, second class currents (SCCs) and uncertainties in the axial and pseudoscalar form factors are calculated for (anti)neutrino induced reaction cross-sections on free nucleon as well as the nucleons bound in a nucleus where nuclear medium effects influence the cross-section. For the nuclear medium effects, we have taken some versions of Fermi gas model (FGM) available in the literature. The results for (anti)neutrino–nucleus scattering cross-section per interacting nucleons are compared with the corresponding results in free nucleon case.
Modeling Mixed Mode Fracture of Concrete by Using the Combined Discrete and Finite Elements Method
Authors: Xu Wei , Zang Mengyan , Sakamoto Jiro
Published: October 2015

The mixed mode (I/II) fracture of concrete is investigated by using a four-point combined discrete and finite elements method. The potential fracture zone is simulated by the discrete elements (DEs) and the other zone by the finite elements (FEs). A cohesive fracture model is employed to simulate the brittle fracture only in the DE subregion. Mesh-size independency of the cohesive fracture model subjected to the DE is carefully investigated with a simple case. Subsequently, the mixed mode fracture behaviors of two simple concrete specimens are simulated and the simulation results achieve good agreements with the other simulations and experimental results.
Construction of energy–momentum tensor of gravitation
Authors: Bamba Kazuharu , Shimizu Katsutaro
Published: October 2015

We construct the gravitational energy–momentum tensor in general relativity through the Noether theorem. In particular, we explicitly demonstrate that the constructed quantity can vary as a tensor under the general coordinate transformation. Furthermore, we verify that the energy–momentum conservation is satisfied because one of the two indices of the energy–momentum tensor should be in the local Lorentz frame. It is also shown that the gravitational energy and the matter one cancel out in certain space-times.
Riemann curvature of a boosted spacetime geometry
Authors: Battista Emmanuele , Esposito Giampiero , Scudellaro Paolo , Tramontano Francesco
Published: October 2015

The ultrarelativistic boosting procedure had been applied in the literature to map the metric of Schwarzschild–de Sitter spacetime into a metric describing de Sitter spacetime plus a shock-wave singularity located on a null hypersurface. This paper evaluates the Riemann curvature tensor of the boosted Schwarzschild–de Sitter metric by means of numerical calculations, which make it possible to reach the ultrarelativistic regime gradually by letting the boost velocity approach the speed of light. Thus, for the first time in the literature, the singular limit of curvature, through Dirac’s [Formula: see text] distribution and its derivatives, is numerically evaluated for this class of spacetimes. Moreover, the analysis of the Kretschmann invariant and the geodesic equation shows that the spacetime possesses a “scalar curvature singularity” within a 3-sphere and it is possible to define what we here call “boosted horizon”, a sort of elastic wall where all particles are surprisingly pushed away, as numerical analysis demonstrates. This seems to suggest that such “boosted geometries” are ruled by a sort of “antigravity effect” since all geodesics seem to refuse to enter the “boosted horizon” and are “reflected” by it, even though their initial conditions are aimed at driving the particles toward the “boosted horizon” itself. Eventually, the equivalence with the coordinate shift method is invoked in order to demonstrate that all [Formula: see text] terms appearing in the Riemann curvature tensor give vanishing contribution in distributional sense.
BENCHMARKING ENTREPRENEURSHIP EDUCATION IN U.S., AUSTRALIAN, AND NEW ZEALAND UNIVERSITY AGRICULTURE PROGRAMS
Authors: MEHLHORN JOEY E. , BONNEY LAURIE , FRASER NIYAN , MILES MORGAN P.
Published: October 2015

The present study examines the extent of entrepreneurship education in Australian, New Zealand and U.S. agricultural colleges and programs. The findings suggest that entrepreneurship is important in agriculture, which is reflected in a majority of programs having some coverage in their curriculum of entrepreneurship. In addition, the courses taught are focused on developing entrepreneurial capabilities such as opportunity recognition and assessment, risk management and networking to create value.
Services and Global Value Chains: Servicification of Manufacturing and Services Networks
Authors: Lanz Rainer , Maurer Andreas
Published: October 2015

The role of services as an input into manufacturing production — often termed "servicification" of manufacturing — is substantial in both developed and developing economies. The paper lays out conceptual and measurement issues related to services networks and provides evidence based on trade in value added statistics. Compared to goods value chains, services networks appear less fragmented internationally based on trade in value added statistics and survey evidence. However, to better capture the international services fragmentation, advances in statistics by enterprise characteristics and by mode of supply, i.e., taking into account the movement of labor and capital, are required.
Scope for ReducingCO2Emissions of Indian Manufacturing: Its Likely Impact on Export Competitiveness
Authors: Goldar Bishwanath , Bhalla Meera
Published: October 2015

This paper explores how reductions in carbon dioxide ( CO2) emissions of Indian manufacturing would impact the export competitiveness of Indian manufacturing firms, by estimating production functions of alternate specifications using data on manufacturing companies for 2007–2008. The results indicate substantial scope for reduction in CO2emissions through factor substitution and reduction in technical inefficiency. The analysis presented in the paper indicates that a reasonable carbon tax of US$ 4–15 per tonne of CO2would cause costs in industrial companies to increase, on average, by 0.36%–1.33% and the consequent loss of exports because of the carbon tax is likely to be small.
Nonnegative Multiresolution Representation-Based Texture Image Classification
Authors: Dong Yongsheng , Tao Dacheng , Li Xuelong
Published: October 2015

Effective representation of image texture is important for an image-classification task. Statistical modelling in wavelet domains has been widely used to image texture representation. However, due to the intraclass complexity and interclass diversity of textures, it is hard to use a predefined probability distribution function to fit adaptively all wavelet subband coefficients of different textures. In this article, we propose a novel modelling approach, Heterogeneous and Incrementally Generated Histogram (HIGH), to indirectly model the wavelet coefficients by use of four local features in wavelet subbands. By concatenating all the HIGHs in all wavelet subbands of a texture, we can construct a nonnegative multiresolution vector (NMV) to represent a texture image. Considering the NMV’s high dimensionality and nonnegativity, we further propose a Hessian regularized discriminative nonnegative matrix factorization to compute a low-dimensional basis of the linear subspace of NMVs. Finally, we present a texture classification approach by projecting NMVs on the low-dimensional basis. Experimental results show that our proposed texture classification method outperforms seven representative approaches.
Conceptual Priming for In-game BCI Training
Authors: Kosmyna Nataliya , Tarpin-Bernard Franck , Rivet Bertrand
Published: October 2015

Using Brain Computer Interfaces (BCIs) as a control modality for games is popular. However BCIs require prior training before playing, which is hurtful to immersion and player experience in the game. For this reason, we propose an explicit integration of the training protocol in game by a modification of the game environment to enforce the synchronicity with the BCI system and to provide appropriate instructions to user. We then dissimulate the synchronicity in the game mechanics by using priming to mask the training instruction (implicit stimuli). We conduct an evaluation of the effects on game experience compared to standard BCI training on 36 subjects. We use the game experience questionnaire (GEQ) coupled with reliability analysis (Cronbach's alpha). The integration does not change the feeling of competence (3/4). However, flow and immersion increase sizably with explicit training integration (2.78 and 2.67/4 from 1.79/4 and 1.52/4) and even more with the implicit training integration (3.27/4 and 3.12/4).
Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice
Authors: Qin Jun , Kandhi Sharath , Froogh Ghezal , Jiang Houli , Luo Meng , Sun Dong , Huang An
Published: October 2015

We hypothesized that potentiating the bioavailability of endothelial epoxyeicosatrienoic acids (EETs) via deletion of the gene for soluble epoxide hydrolase (sEH), or downregulation of sEH expression, enhances flow/shear stress-induced dilator responses (FID) of arterioles. With the use of male (M) and female (F) wild-type (WT) and sEH-knockout (KO) mice, isolated gracilis muscle arterioles were cannulated and pressurized at 80 mmHg. Basal tone and increases in diameter of arterioles as a function of perfusate flow (5, 10, 15, 20, and 25 μl/min) were recorded. The magnitude of FID was significantly smaller and associated with a greater arteriolar tone in M-WT than F-WT mice, revealing a sex difference in FID. This sex difference was abolished by deletion of the sEH gene, as evidenced by an enhanced FID in M-KO mice to a level comparable with those observed in F-KO and F-WT mice. These three groups of mice coincidentally exhibited an increased endothelial sensitivity to shear stress (smaller WSS50) and were hypotensive. Endothelial EETs participated in the mediation of enhanced FID in M-KO, F-KO, and F-WT mice, without effects on FID of M-WT mice. Protein expression of sEH was downregulated by approximately fourfold in vessels of F-WT compared with M-WT mice, paralleled with greater vascular EET levels that were statistically comparable with those observed in both male and female sEH-KO mice. In conclusion, sex-different regulation of sEH accounts for sex differences in flow-mediated dilation of microvessels in gonadally intact mice.
The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium
Authors: Milani-Nejad Nima , Canan Benjamin D. , Elnakish Mohammad T. , Davis Jonathan P. , Chung Jae-Hoon , Fedorov Vadim V. , Binkley Philip F. , Higgins Robert S. D. , Kilic Ahmet , Mohler Peter J. , Janssen Paul M. L.
Published: October 2015

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing ( n = 9) and failing ( n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae ( n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization ( P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment ( ktr) in both nonfailing and failing myocardium ( P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length ( P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/d t slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients.
Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+ influx in airway smooth muscle cells
Authors: Song Tengyao , Hao Qiongyu , Zheng Yun-Min , Liu Qing-Hua , Wang Yong-Xiao
Published: October 2015

Transient receptor potential-3 (TRPC3) channels play a predominant role in forming nonselective cation channels (NSCCs) in airway smooth muscle cells (ASMCs) and are significantly increased in their activity and expression in asthmatic ASMCs. To extend these novel findings, we have explored the regulatory mechanisms that control the activity of TRPC3 channels. Our data for the first time reveal that inositol 1,4,5-trisphosphate (IP3), an important endogenous signaling molecule, can significantly enhance the activity of single NSCCs in ASMCs. The analog of diacylglycerol (DAG; another endogenous signaling molecule), 1-oleyl-2-acetyl- sn-glycerol (OAG), 1-stearoyl-2-arachidonoyl- sn-glycerol (SAG), and 1-stearoyl-2-linoleoyl- sn-glycerol (SLG) all augment NSCC activity. The effects of IP3 and OAG are fully abolished by lentiviral short-hairpin (sh)RNA-mediated TRPC3 channel knockdown (KD). The stimulatory effect of IP3 is eliminated by heparin, an IP3 receptor (IP3R) antagonist that blocks the IP3-binding site, but not by xestospongin C, the IP3R antagonist that has no effect on the IP3-binding site. Lentiviral shRNA-mediated KD of IP3R1, IP3R2, or IP3R3 does not alter the excitatory effect of IP3. TRPC3 channel KD greatly inhibits IP3-induced increase in intracellular Ca2+ concentration. IP3R1 KD produces a similar inhibitory effect. TRPC3 channel and IP3R1 KD both diminish the muscarinic receptor agonist methacholine-evoked Ca2+ responses. Taking these findings together, we conclude that IP3, the important intracellular second messenger, may activate TRPC3 channels to cause extracellular Ca2+ influx, in addition to opening IP3Rs to induce intracellular Ca2+ release. This novel extracellular Ca2+ entry route may play a significant role in mediating IP3-mediated numerous cellular responses in ASMCs and other cells.
Dual Roles of RNF2 in Melanoma Progression
Authors: Rai Kunal , Akdemir Kadir C. , Kwong Lawrence N. , Fiziev Petko , Wu Chang-Jiun , Keung Emily Z. , Sharma Sneha , Samant Neha S. , Williams Maura , Axelrad Jacob B. , Shah Amiksha , Yang Dong , Grimm Elizabeth A. , Barton Michelle C. , Milton Denai R. , Heffernan Timothy P. , Horner James W. , Ekmekcioglu Suhendan , Lazar Alexander J. , Ernst Jason , Chin Lynda
Published: October 2015

Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling. In contrast, RNF2′s oncogenic activity does not require its catalytic activity nor does it derive from its canonical gene repression function. Instead, RNF2 drives proliferation through direct transcriptional upregulation of the cell-cycle regulator CCND2. We further show that MEK1-mediated phosphorylation of RNF2 promotes recruitment of activating histone modifiers UTX and p300 to a subset of poised promoters, which activates gene expression. In summary, RNF2 regulates distinct biologic processes in the genesis and progression of melanoma via different molecular mechanisms.

Significance: The role of epigenetic regulators in cancer progression is being increasingly appreciated. We show novel roles for RNF2 in melanoma tumorigenesis and metastasis, albeit via different mechanisms. Our findings support the notion that epigenetic regulators, such as RNF2, directly and functionally control powerful gene networks that are vital in multiple cancer processes. Cancer Discov; 5(12); 1314–27. ©2015 AACR.

See related commentary by Black and Whetstine, p. 1241.

This article is highlighted in the In This Issue feature, p. 1225
Effect of the Probiotic Lactobacillus rhamnosus LB21 on the Cariogenicity of Streptococcus mutans UA159 in a Dual-Species Biofilm Model
Authors: Fernández Constanza E. , Giacaman Rodrigo A. , Tenuta Livia M. , Cury Jaime A.
Published: October 2015

Despite promising results using probiotics, evidence of the preventive effect on enamel demineralization is insufficient and the cariogenic potential of probiotics is still controversial. Probiotics could affect biofilm formation and interfere with adherence, growth or coaggregation with Streptococcus mutans in biofilms. However, most of the studies have been conducted using planktonic bacteria. Hence, the aim of the study was to assess the effect of probiotic bacteria on the cariogenicity of S. mutans using an in vitro biofilm caries model on enamel. Single-species biofilms (S. mutans UA159, SM or Lactobacillus rhamnosus LB21, LB) or dual-species biofilms simultaneously inoculated (SM + LB) or LB inoculated 8 h after SM (SM → LB) were grown for 96 h. Biofilms were formed on bovine enamel saliva-coated slabs of known surface hardness (SH) and immersed in culture media. Biofilms were exposed 8 times per day to 10% sucrose. Medium pH was monitored twice daily as a biofilm acidogenicity indicator. After 96 h, biofilms were collected to determine biomass and bacteria viability. Slab demineralization was calculated as percentage of SH loss (%SHL). Additionally, the model was tested with different concentrations of the initial inoculum (103, 106, 108 cells/ml) and different adhesion times (2 or 8 h). The dual-species biofilm revealed no LB effects on SM cariogenicity, without changes in acidogenicity or %SHL among groups (p > 0.05, n = 12). Lack of activity of LB on SM cariogenicity persisted even when 105 times higher concentration of the probiotic was tested. Coaggregation was not observed. In conclusion, findings suggest that LB does not reduce cariogenicity of SM in a validated experimental caries model.
Large Papillomatous and Pedunculated Nevus Sebaceous
Authors: Ubol Taksaorn , Aunhachoke Kobkul
Published: October 2015

We present a 6-week-old female infant from the Lao People's Democratic Republic with a large, red, exophytic scalp mass and numerous flesh-colored verrucous plaques on her face and the right half of her body since birth. The clinical and pathological findings are consistent with the new phenotype of the large, polypoid types of nevus sebaceous.
A transmissão televisiva da narração de uma partida de futebol como texto sincrético
Authors: Madrid Rodrigo Lazaresko
Published: October 2015

O objetivo deste artigo é demonstrar como a transmissão de uma partida de futebol pode ser compreendida e analisada como um texto sincrético (Fiorin, 2009), uma vez que combina aspectos visuais e verbais em um único enunciado audiovisual. Para isso, apresenta-se a análise inicial de um trecho da transmissão da partida entre Corinthians e Chelsea, emitida no dia 16 de dezembro de 2012 pela Rede Globo de televisão, com narração de Galvão Bueno. O trecho analisado exibe uma jogada que culmina em gol, bem como alguns instantes que o sucedem. Esse momento de gol é compreendido como um programa narrativo, conforme demonstra Carmo Júnior (2005). Ao buscar identificar quais são os atores que figurativizam os papéis actanciais da narrativa, observa-se aquilo que Hjelmslev (1975) chama de “fusão”, um modo de sincretismo. A depender do ponto de vista adotado (com base em cada uma das equipes), a narração pode: (i) partir de um estado disjuntivo e atingir um estado conjuntivo com a conquista do gol; ou (ii) partir de um estado conjuntivo de estabilidade e atingir um estado disjuntivo, com o gol sofrido. As figuras do discurso podem, então, desempenhar as funções de sujeito e de antissujeito simultaneamente. Outro aspecto sincrético da transmissão televisiva diz respeito às substâncias verbais e visuais presentes. O artigo busca mostrar como esses aspectos contribuem sincreticamente para o percurso narrativo, em termos de duração, altura, tempo e intensidade.
Afirmação da identidade no texto “Bonecas pretas do quilombo de Conceição das Crioulas”
Authors: Vilela Ilca Suzana Lopes
Published: October 2015

Neste artigo, sob a perspectiva da semiótica greimasiana, refletimos sobre a seguinte questão: O o que é e como se produz o efeito de sentido de afirmação da identidade? A partir de discussão teórica e de sua incidência na análise do texto bonecas pretas do Quilombo de Conceição das Crioulas, observamos que a identidade semiótica é um simulacro e para o efeito de sua afirmação são necessários elementos sintáxicos que produzam a repetição que, no discurso das bonecas, realiza-se, principalmente, com o recurso à isotopia, à aspectualização e à tensividade.
Epigenetic Control of Smooth Muscle Cell Identity and Lineage Memory
Authors: Gomez Delphine , Swiatlowska Pamela , Owens Gary K.
Published: October 2015

Vascular smooth muscle cells (SMCs), like all cells, acquire a cell-specific epigenetic signature during development that includes acquisition of a unique repertoire of histone and DNA modifications. These changes are postulated to induce an open chromatin state (referred to as euchromatin) on the repertoire of genes that are expressed in differentiated SMC, including SMC-selective marker genes like Acta2 and Myh11, as well as housekeeping genes expressed by most cell types. In contrast, genes that are silenced in differentiated SMC acquire modifications associated with a closed chromatin state (ie, heterochromatin) and transcriptional silencing. Herein, we review mechanisms that regulate epigenetic control of the differentiated state of SMC. In addition, we identify some of the major limitations in the field and future challenges, including development of innovative new tools and approaches, for performing single-cell epigenetic assays and locus-selective editing of the epigenome that will allow direct studies of the functional role of specific epigenetic controls during development, injury repair, and disease, including major cardiovascular diseases, such as atherosclerosis, hypertension, and microvascular disease, associated with diabetes mellitus.
White Matter Lesion Progression
Authors: Hofer Edith , Cavalieri Margherita , Bis Joshua C. , DeCarli Charles , Fornage Myriam , Sigurdsson Sigurdur , Srikanth Velandai , Trompet Stella , Verhaaren Benjamin F.J. , Wolf Christiane , Yang Qiong , Adams Hieab H.H. , Amouyel Philippe , Beiser Alexa , Buckley Brendan M. , Callisaya Michele , Chauhan Ganesh , de Craen Anton J.M. , Dufouil Carole , van Duijn Cornelia M. , Ford Ian , Freudenberger Paul , Gottesman Rebecca F. , Gudnason Vilmundur , Heiss Gerardo , Hofman Albert , Lumley Thomas , Martinez Oliver , Mazoyer Bernard , Moran Chris , Niessen Wiro J. , Phan Thanh , Psaty Bruce M. , Satizabal Claudia L. , Sattar Naveed , Schilling Sabrina , Shibata Dean K. , Slagboom P. Eline , Smith Albert , Stott David J. , Taylor Kent D. , Thomson Russell , Töglhofer Anna M. , Tzourio Christophe , van Buchem Mark , Wang Jing , Westendorp Rudi G.J. , Gwen Windham B. , Vernooij Meike W. , Zijdenbos Alex , Beare Richard , Debette Stéphanie , Ikram M. Arfan , Jukema J. Wouter , Launer Lenore J. , Longstreth W. T. , Mosley Thomas H. , Seshadri Sudha , Schmidt Helena , Schmidt Reinhold
Published: October 2015

Background and Purpose—

White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

Methods—

Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies.

Results—

A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (
P
<5×10
−8
). Four loci were suggestive (
P
<1×10
−5
) of an association with WML progression: 10q24.32 (rs10883817,
P
=1.46×10
−6
); 12q13.13 (rs4761974,
P
=8.71×10
−7
); 20p12.1 (rs6135309,
P
=3.69×10
−6
); and 4p15.31 (rs7664442,
P
=2.26×10
−6
). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden.

Conclusions—

Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.
Carotid Plaque Morphology Is Significantly Associated With Sex, Age, and History of Neurological Symptoms
Authors: Wendorff Carina , Wendorff Heiko , Pelisek Jaroslav , Tsantilas Pavlos , Zimmermann Alexander , Zernecke Alma , Kuehnl Andreas , Eckstein Hans-Henning
Published: October 2015

Background and Purpose—

The purpose of this study was to analyze the association between morphological characteristics of human carotid plaques and patient’s sex, age, and history of neurological symptoms.

Methods—

The study included 763 atherosclerotic plaques from patients treated surgically for carotid stenosis between 2004 and 2013. Histological analyses of carotid plaques were performed to assess the type of plaque (American Heart Association classification), the stability of the plaque, the extent of calcification, inflammation, and neovascularization, as well as the deposition of collagen and elastin. According to the scale of outcome measurement, logistic regression, ordinal regression, and multinomial regression analyses were applied. All results were adjusted for common risk factors of atherosclerosis.

Results—

Male sex was associated with more cellularity (odds ratio [OR], 1.56;
P
=0.003), more inflammatory infiltrates (OR, 1.75;
P
<0.001), and more neovascularization (OR, 1.47;
P
=0.010), but less calcification (OR, 0.78;
P
=0.090). Symptomatic patients were more likely to have a lower amount of elastin (OR, 0.71;
P
=0.057). Higher age was associated with increased calcification (OR, 1.23;
P
=0.009). Unstable plaques were found more frequently in symptomatic patients (OR, 1.60; 95% confidence interval, 1.14–2.25;
P
=0.007). A multinomial regression model revealed that age, sex, and history of neurological symptoms were significantly associated with specific plaque types (
P
=0.009,
P
<0.001, and
P
=0.017, respectively).

Conclusions—

Plaque morphology differed between men and women and varied with age. Certain types of plaques (VI and VI/VII) as well as unstable plaques were significantly associated with a history of neurological symptoms. Thus, individual approaches (eg, in detection of plaque hemorrhage or thin fibrous caps) especially based on sex and age should be considered to identify patients at increased risk of stroke.
Visualizing Rayleigh Scattering through UV Photography
Authors: Lindfors Anders V. , Ylianttila Lasse
Published: October 2015

A tailored camera setup has been used to take photographs of the atmosphere and the environment as seen in the ultraviolet (UV) wavelength band. These photographs make visible what the human eye cannot normally perceive—in particular, the effects of the increasingly strong scattering of UV radiation by the molecular atmosphere. This scattering of sunlight by air molecules is commonly known as Rayleigh scattering, and its scattering efficiency is inversely proportional to the fourth power of the wavelength; the shorter the wavelength, the stronger the scattering. The blue color of the cloud-free sky is a well-known consequence of this, while it is also known that radiation in the UV band is even more diffuse than blue light. The UV photographs presented here demonstrate these effects of Rayleigh scattering. They show, for example, how clouds are much harder to distinguish from the background (the sky) in the UV than in the visible band, and how shadows tend to disappear in the UV. Thereby, these photographs provide intuitive insight into the physics of Rayleigh scattering, and help connect the typically abstract and theoretical information of textbooks and scientific articles with a more concrete understanding of the effects of Rayleigh scattering.
Storm-Scale Data Assimilation and Ensemble Forecasting with the NSSL Experimental Warn-on-Forecast System. Part I: Radar Data Experiments
Authors: Wheatley Dustan M. , Knopfmeier Kent H. , Jones Thomas A. , Creager Gerald J.
Published: October 2015

This first part of a two-part study on storm-scale radar and satellite data assimilation provides an overview of a multicase study conducted as part of the NOAA Warn-on-Forecast (WoF) project. The NSSL Experimental WoF System for ensembles (NEWS-e) is used to produce storm-scale analyses and forecasts of six diverse severe weather events from spring 2013 and 2014. In this study, only Doppler reflectivity and radial velocity observations (and, when available, surface mesonet data) are assimilated into a 36-member, storm-scale ensemble using an ensemble Kalman filter (EnKF) approach. A series of 1-h ensemble forecasts are then initialized from storm-scale analyses during the 1-h period preceding the onset of storm reports. Of particular interest is the ability of these 0–1-h ensemble forecasts to reproduce the low-level rotational characteristics of supercell thunderstorms, as well as other convective hazards. For the tornado-producing thunderstorms considered in this study, ensemble probabilistic forecasts of low-level rotation generally indicated a rotating thunderstorm approximately 30 min before the time of first observed tornado. Displacement errors (often to the north of tornado-affected areas) associated with vorticity swaths were greatest in those forecasts launched 30–60 min before the time of first tornado. Similar forecasts were produced for a tornadic mesovortex along the leading edge of a bow echo and, again, highlighted a well-defined vorticity swath as much as 30 min prior to the first tornado.
The Role of Collective Efficacy in Climate Change Adaptation in India
Authors: Thaker Jagadish , Maibach Edward , Leiserowitz Anthony , Zhao Xiaoquan , Howe Peter
Published: October 2015

Research on adaptive capacity often focuses on economics and technology, despite evidence from the social sciences finding that socially shared beliefs, norms, and networks are critical in increasing individuals’ and communities’ adaptive capacity. Drawing upon social cognitive theory, this paper builds on the first author’s Ph.D. dissertation and examines the role of collective efficacy—people’s shared beliefs about their group’s capabilities to accomplish collective tasks—in influencing Indians’ capacity to adapt to drinking water scarcity, a condition likely to be exacerbated by future climate change. Using data from a national survey (N = 4031), individuals with robust collective efficacy beliefs were found to be more likely to participate in community activities intended to ensure the adequacy of water supplies, and this relationship was found to be stronger in communities with high levels of community collective efficacy compared to communities with low levels of community collective efficacy. In addition, community collective efficacy was positively associated with self-reported community adaptation responses. Public education campaigns aimed at increasing collective efficacy beliefs are likely to increase adaptive capacity.
The revenge motive in delinquency
Authors: Kivivuori Janne , Savolainen Jukka , Aaltonen Mikko
Published: October 2015

Revenge is a well-recognised motive for crime and violence. In sociological research, this topic has been pursued primarily in ethnographic studies of street offenders or gang conflicts. Psychologists have studied revenge behaviour experimentally in laboratory settings and revenge ideation with community samples. Despite these contributions, we know very little about the prevalence and correlates of revenge-motivated offending in representative mainstream population. Most studies focus on violence, ignoring the role revenge may play in non-violent offending. Drawing on a Finnish youth crime survey ( n = 5373), this research describes the prevalence of the revenge motive in delinquent behaviour and explores correlates of revenge-motivated delinquency (RMD). The findings indicate that approximately one-half of interpersonal assaults are motivated by revenge and that a significant proportion (10–20%) of running away from home and vandalism is also related to revenge. Narrative evidence from incident descriptions suggests that roughly one in four RMD incidents reflect social/altruistic offending on behalf of a friend or a relative. In correlational analysis, girls, victims of school bullying and those expressing pro-revenge attitudes were more likely to be motivated by revenge when engaging in delinquency. The findings suggest that social learning, situational strain and deterrence theories are promising directions for further research in this area.