bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroacupuncture Ameliorates Propofol-Induced Cognitive Impairment via an Opioid Receptor-Independent Mechanism
Authors: Liu Yan , Wang Xin-Juan , Wang Na , Cui Cai-Lian , Wu Liu-Zhen
Published: May 2016

While general anesthesia is known to induce cognitive deficits in elderly and pediatric patients, its influence on adults is less well-characterized. The present study was designed to evaluate the influence of propofol on the learning and memory of young adult rats, as well as the potential neuroprotective role of electroacupuncture (EA) in propofol-induced cognitive impairment. Intravenous anesthesia with propofol was administered to young adult male Sprague–Dawley (SD) rats for 6 h, and EA was administered three times before and after anesthesia. The Morris Water Maze (MWM) test was conducted to determine the rat’s cognitive performance following the anesthesia treatment. Our results showed that propofol induced obvious cognitive impairment in young adult rats, which could be ameliorated by multiple EA treatments. Moreover, the decreased level of phosphorylated glycogen synthase kinase 3 β (pGSK-3β) in the CA1 region of the hippocampus accompanying the cognitive impairment was also reversed by EA treatment. Further experiments demonstrated that neither 2 nor 10 mg/kg (I.P.) naloxone blocked the effect of EA, indicating that the neuroprotective effect of EA on propofol-induced cognitive impairment was not mediated via the opioid receptors. The present study suggests that EA could ameliorate the cognitive impairment induced by prolonged anesthesia with propofol in young adult rats, which is likely associated with pGSK-3β levels in the CA1 independently of opioid receptors. These findings imply that EA may be used as a potential neuroprotective therapy for post-operative cognitive dysfunction (POCD).
Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats
Authors: Shao Jingyun , Wang Peng , Liu An , Du Xusheng , Bai Jie , Chen Mingwei
Published: May 2016

Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol’s scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.
Effects ofPanax notoginsengon the Metastasis of Human Colorectal Cancer Cells
Authors: Hsieh Shu-Ling , Hsieh Shuchen , Kuo Yu-Hao , Wang Jyh-Jye , Wang Jinn-Chyi , Wu Chih-Chung
Published: May 2016

The goal of this study was to investigate the effect of the Panax notoginseng ethanol extract (PNEE) on the regulation of human colorectal cancer (CRC) metastasis. The migratory, invasive, and adhesive abilities and the expression of metastasis-associated regulatory molecules in cultured human CRC cells (HCT-116) treated with the PNEE were analyzed in this study. The migratory and invasive abilities of HCT-116 cells were reduced after PNEE treatment. The incubation of HCT-116 cells with the PNEE for 24 h decreased MMP-9 expression and increased E-cadherin expression compared with the control group. The adhesion reaction assay indicated that treatment with the PNEE led to significantly decreased HCT-116 adhesion to endothelial cells (EA.hy926 cells). The integrin-1 protein levels in HCT-116 cells were significantly decreased following treatment with the PNEE. Similarly, the protein levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased by treatment of the EA.hy926 endothelial cells with PNEE. A scanning electron microscope (SEM) examination indicated that HCT-116 cells treated with LPS combined with the PNEE had a less flattened and retracted shape compared with LPS-treated cells, and this change in shape was found to be a phenomenon of extravasation invasion. The transepithelial electrical resistance (TEER) of the EA.hy926 endothelial cell monolayer increased after incubation with the PNEE for 24 h. A cell-cell permeability assay indicated that HCT-116 cells treated with the PNEE displayed significantly reduced levels of phosphorylated VE-cadherin (p-VE-cadherin). These results demonstrate the antimetastatic properties of the PNEE and show that the PNEE affects cells by inhibiting cell migration, invasion, and adhesion and regulating the expression of metastasis-associated signaling molecules.
Cytotoxicity ofSalvia miltiorrhizaAgainst Multidrug-Resistant Cancer Cells
Authors: Wu Ching-Fen , Bohnert Stefan , Thines Eckhard , Efferth Thomas
Published: May 2016

Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavage of caspase 3, 7, 9 and poly ADP-ribose polymerase (PARP). MAP kinases including JNK, ERK1/2 and p38 were obviously phosphorylated and nuclear P65 was downregulated upon SM treatment. Transcriptome-wide COMPARE analysis revealed that the expression of encoding genes with diverse functions were associated with the cellular response to cryptotanshinone, one of the main constituents of SM root extract. In conclusion, SM root extract exerted profound cytotoxicity towards various sensitive and resistant cancer cells and induced the intrinsic apoptotic pathway.
Inertial mass from Unruh temperatures
Authors: Giné J. , McCulloch M. E.
Published: May 2016

It has been proposed that inertia can be explained as follows: when objects accelerate in one direction, a Rindler horizon forms in the other direction suppressing Unruh radiation on that side and producing a net Unruh radiation pressure that always opposes the acceleration, just like inertia. So far, this model has predicted masses over twice those expected. In this paper, an error in this model is corrected so that its prediction improves to within 29% of the expected Planck mass. It is also shown that inertial mass may be understood qualitatively by applying Carnot’s principle and entropy to Unruh temperatures, so that the work needed for inertia comes from the difference in the Unruh temperatures seen by the accelerated object and the cosmos. This implies that highly-accelerated systems may emit heat in a new way.
Algorithm 958
Authors: L'ecuyer Pierre , Munger David
Published: May 2016

We introduce a new software tool and library named Lattice Builder, written in C++, that implements a variety of construction algorithms for good rank-1 lattice rules. It supports exhaustive and random searches, as well as component-by-component (CBC) and random CBC constructions, for any number of points, and for various measures of (non)uniformity of the points. The measures currently implemented are all shift-invariant and represent the worst-case integration error for certain classes of integrands. They include, for example, the weighted Pα square discrepancy, the Rα criterion, and figures of merit based on the spectral test, with projection-dependent weights. Each of these measures can be computed as a finite sum. For the Pα and Rα criteria, efficient specializations of the CBC algorithm are provided for projection-dependent, order-dependent, and product weights. For numbers of points that are integer powers of a prime base, the construction of embedded rank-1 lattice rules is supported through any of these algorithms, and through a fast CBC algorithm, with a variety of possibilities for the normalization of the merit values of individual embedded levels and for their combination into a single merit value. The library is extensible, thanks to the decomposition of the algorithms into decoupled components, which makes it easy to implement new types of weights, new search domains, new figures of merit, and so on.
Biomedical Ontology Quality Assurance Using a Big Data Approach
Authors: Cui Licong , Tao Shiqiang , Zhang Guo-Qiang
Published: May 2016

This article presents recent progresses made in using scalable cloud computing environment, Hadoop and MapReduce, to perform ontology quality assurance (OQA), and points to areas of future opportunity. The standard sequential approach used for implementing OQA methods can take weeks if not months for exhaustive analyses for large biomedical ontological systems. With OQA methods newly implemented using massively parallel algorithms in the MapReduce framework, several orders of magnitude in speed-up can be achieved (e.g., from three months to three hours). Such dramatically reduced time makes it feasible not only to perform exhaustive structural analysis of large ontological hierarchies, but also to systematically track structural changes between versions for evolutional analysis. As an exemplar, progress is reported in using MapReduce to perform evolutional analysis and visualization on the Systemized Nomenclature of Medicine—Clinical Terms (SNOMED CT), a prominent clinical terminology system. Future opportunities in three areas are described: one is to extend the scope of MapReduce-based approach to existing OQA methods, especially for automated exhaustive structural analysis. The second is to apply our proposed MapReduce Pipeline for Lattice-based Evaluation (MaPLE) approach, demonstrated as an exemplar method for SNOMED CT, to other biomedical ontologies. The third area is to develop interfaces for reviewing results obtained by OQA methods and for visualizing ontological alignment and evolution, which can also take advantage of cloud computing technology to systematically pre-compute computationally intensive jobs in order to increase performance during user interactions with the visualization interface. Advances in these directions are expected to better support the ontological engineering lifecycle.
Mining Dual Networks
Authors: WU Yubao , Zhu Xiaofeng , Li Li , Fan Wei , Jin Ruoming , Zhang Xiang
Published: May 2016

Finding the densest subgraph in a single graph is a fundamental problem that has been extensively studied. In many emerging applications, there exist
dual
networks. For example, in genetics, it is important to use protein interactions to interpret genetic interactions. In this application, one network represents
physical
interactions among nodes, for example, protein--protein interactions, and another network represents
conceptual
interactions, for example, genetic interactions. Edges in the conceptual network are usually derived based on certain correlation measure or statistical test measuring the strength of the interaction. Two nodes with strong conceptual interaction may not have direct physical interaction.

In this article, we propose the novel dual-network model and investigate the problem of finding the densest connected subgraph (DCS), which has the largest density in the conceptual network and is also connected in the physical network. Density in the conceptual network represents the average strength of the measured interacting signals among the set of nodes. Connectivity in the physical network shows how they interact physically. Such pattern cannot be identified using the existing algorithms for a single network. We show that even though finding the densest subgraph in a single network is polynomial time solvable, the DCS problem is NP-hard. We develop a two-step approach to solve the DCS problem. In the first step, we effectively prune the dual networks, while guarantee that the optimal solution is contained in the remaining networks. For the second step, we develop two efficient greedy methods based on different search strategies to find the DCS. Different variations of the DCS problem are also studied. We perform extensive experiments on a variety of real and synthetic dual networks to evaluate the effectiveness and efficiency of the developed methods.
Unsupervised Rare Pattern Mining
Authors: Koh Yun Sing , Ravana Sri Devi
Published: May 2016

Association rule mining was first introduced to examine patterns among frequent items. The original motivation for seeking these rules arose from need to examine customer purchasing behaviour in supermarket transaction data. It seeks to identify combinations of items or itemsets, whose presence in a transaction affects the likelihood of the presence of another specific item or itemsets. In recent years, there has been an increasing demand for rare association rule mining. Detecting rare patterns in data is a vital task, with numerous high-impact applications including medical, finance, and security. This survey aims to provide a general, comprehensive, and structured overview of the state-of-the-art methods for rare pattern mining. We investigate the problems in finding rare rules using traditional association rule mining. As rare association rule mining has not been well explored, there is still specific groundwork that needs to be established. We will discuss some of the major issues in rare association rule mining and also look at current algorithms. As a contribution, we give a general framework for categorizing algorithms: Apriori and Tree based. We highlight the differences between these methods. Finally, we present several real-world application using rare pattern mining in diverse domains. We conclude our survey with a discussion on open and practical challenges in the field.
Counting Homomorphisms to Square-Free Graphs, Modulo 2
Authors: Göbel Andreas , Goldberg Leslie Ann , Richerby David
Published: May 2016

We study the problem ⊕H
oms
T
o
H
of counting, modulo 2, the homomorphisms from an input graph to a fixed undirected graph
H
. A characteristic feature of modular counting is that cancellations make wider classes of instances tractable than is the case for exact (nonmodular) counting; thus, subtle dichotomy theorems can arise. We show the following dichotomy: for any
H
that contains no 4-cycles, ⊕H
oms
T
o
H
is either in polynomial time or is ⊕P-complete. This partially confirms a conjecture of Faben and Jerrum that was previously only known to hold for trees and for a restricted class of tree-width-2 graphs called cactus graphs. We confirm the conjecture for a rich class of graphs, including graphs of unbounded tree-width. In particular, we focus on square-free graphs, which are graphs without 4-cycles. These graphs arise frequently in combinatorics, for example, in connection with the strong perfect graph theorem and in certain graph algorithms. Previous dichotomy theorems required the graph to be tree-like so that tree-like decompositions could be exploited in the proof. We prove the conjecture for a much richer class of graphs by adopting a much more general approach.
Mining Privacy Goals from Privacy Policies Using Hybridized Task Recomposition
Authors: Bhatia Jaspreet , Breaux Travis D. , Schaub Florian
Published: May 2016

Privacy policies describe high-level goals for corporate data practices; regulators require industries to make available conspicuous, accurate privacy policies to their customers. Consequently, software requirements must conform to those privacy policies. To help stakeholders extract privacy goals from policies, we introduce a semiautomated framework that combines crowdworker annotations, natural language typed dependency parses, and a reusable lexicon to improve goal-extraction coverage, precision, and recall. The framework evaluation consists of a five-policy corpus governing web and mobile information systems, yielding an average precision of 0.73 and recall of 0.83. The results show that no single framework element alone is sufficient to extract goals; however, the overall framework compensates for elemental limitations. Human annotators are highly adaptive at discovering annotations in new texts, but those annotations can be inconsistent and incomplete; dependency parsers lack sophisticated, tacit knowledge, but they can perform exhaustive text search for prospective requirements indicators; and while the lexicon may never completely saturate, the lexicon terms can be reliably used to improve recall. Lexical reuse reduces false negatives by 41%, increasing the average recall to 0.85. Last, crowd workers were able to identify and remove false positives by around 80%, which improves average precision to 0.93.
elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves
Authors: Guo Zhi-Ling , Longhurst John C. , Tjen-A-Looi Stephanie C. , Fu Liang-Wu
Published: May 2016

The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation ( P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated ( n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation ( n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM ( n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway.
Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia
Authors: Al-Mughales Jamil A.
Published: May 2016

Objective.To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies.Methods.Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies.Results.A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796–0.837) versus 0.770 (95% CI = 0.707–0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude.Conclusion.Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history.
Traditional Chinese Medicine for Metabolic Syndrome via TCM Pattern Differentiation: Tongue Diagnosis for Predictor
Authors: Lee Tsung-Chieh , Lo Lun-Chien , Wu Fang-Chen
Published: May 2016

Metabolic syndrome is a morbid condition, which is manifested by central obesity, abnormal glucose tolerance, lipodystrophy, and hypertension. Traditional Chinese medicine (TCM) clarifies that obesity is classified as phlegm‐dampness. It is often accompanied with qi stagnation and blood stasis. One hundred and two overweight adults, who did not receive lipid‐lowering drugs, were enrolled for analysis. The exclusion criteria were adults having malignancy disease, DM, and renal disease or who were pregnant or lactating. The study was divided into two groups: metabolic syndrome group (MetS) and nonmetabolic syndrome group (nMetS). The modern tongue analysis and heart rate variability devices for data analysis and Council on Nutrition Appetite Questionnaire (CNAQ) for appetite evaluation were used. Obesity patients with metabolic syndrome obviously have lower CNAQ score. The 6 items of CNAQ between two groups have significant difference in variation (P < 0.001). The nMetS average was above 28 scores (96%) and the MetS was all in 17–28 scores. The tongue appearance showed that MetS group have white coating different from the nMetS group with white and yellow coating (P < 0.05). However the HRV is not different from nMetS group significantly. Our results try to explore the relationship between the TCM pattern, nutrition appetite, and heart rate variability in metabolic syndrome patients.
Unraveling the Limits of Mitochondrial Control Region to Estimate the Fine Scale Population Genetic Differentiation in Anadromous FishTenualosa ilisha
Authors: Verma Rashmi , Singh Mahender , Kumar Sudhir
Published: May 2016

The mitochondrial control region has been the first choice for examining the population structure but hypervariability and homoplasy have reduced its suitability. We analysed eight populations using control region for examining the population structure ofHilsa. Although the control region analysis revealed broad structuring between the Arabian Sea and Bay of Bengal (FST  0.0441,p<0.001) it was unable to detect structure among riverine populations. These results suggest that the markers used must be able to distinguish populations and control region has led to an underestimation of genetic differentiation among populations ofHilsa.
Brain Connectomics’ Modification to Clarify Motor and Nonmotor Features of Myotonic Dystrophy Type 1
Authors: Serra Laura , Mancini Matteo , Silvestri Gabriella , Petrucci Antonio , Masciullo Marcella , Spanò Barbara , Torso Mario , Mastropasqua Chiara , Giacanelli Manlio , Caltagirone Carlo , Cercignani Mara , Meola Giovanni , Bozzali Marco
Published: May 2016

The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients’ brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool.
Effect of Na Doping on the Nanostructures and Electrical Properties of ZnO Nanorod Arrays
Authors: Yue Lu , Zhang Zhiqiang , Ma Yanyan , Zhang Wenhui
Published: May 2016

The p-type ZnO nanorod arrays were prepared by doping Na with hydrothermal method. The structural, electrical, and optical properties were explored by XRD, Hall-effect, PL, and Raman spectra. The carrier concentrations and the mobility of Na-doped ZnO nanorod arrays are arranged from1.4×1016 cm−3to1.7×1017 cm−3and 0.45 cm2 v−1 s−1to 106 cm2 v−1 s−1, respectively.
DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers
Authors: Schupp Nicole , Stopper Helga , Heidland August
Published: May 2016

Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients’ burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis‐block micronucleus assay, the comet assay, and the quantification of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker’s potential to predict clinical outcomes.
Stagnation Point Flow of Nanofluid over a Moving Plate with Convective Boundary Condition and Magnetohydrodynamics
Authors: Mabood Fazle , Pochai Nopparat , Shateyi Stanford
Published: May 2016

A theoretical investigation is carried out to examine the effects of volume fraction of nanoparticles, suction/injection, and convective heat and mass transfer parameters on MHD stagnation point flow of water-based nanofluids (Cu and Ag). The governing partial differential equations for the fluid flow, temperature, and concentration are reduced to a system of nonlinear ordinary differential equations. The derived similarity equations and corresponding boundary conditions are solved numerically using Runge-Kutta Fehlberg fourth-fifth order method. To exhibit the effect of the controlling parameters on the dimensionless velocity, temperature, nanoparticle volume fraction, skin friction factor, and local Nusselt and local Sherwood numbers, numerical results are presented in graphical and tabular forms. It is found that the friction factor and heat and mass transfer rates increase with magnetic field and suction/injection parameters.
Pioglitazone Effect on Glioma Stem Cell Lines: Really a Promising Drug Therapy for Glioblastoma?
Authors: Cilibrasi Chiara , Butta Valentina , Riva Gabriele , Bentivegna Angela
Published: May 2016

Glioblastoma multiforme (GBM) represents one of the most frequent malignant brain tumors. Current therapies do not provide real solutions to this pathology. Their failure can be ascribed to a cell subpopulation with stem-like properties called glioma stem cells (GSCs). Therefore, new therapeutic strategies GSC-targeted are needed. PPARγ, a nuclear receptor involved in lipid metabolism, has already been indicated as a promising target for antineoplastic therapies. Recent studies have reported that synthetic PPARγagonists, already in clinical use for the treatment of type II diabetes, exhibit antineoplastic effects in a wide range of malignant tumor cells, including glioma cells. We investigated the effect of the synthetic PPARγagonist Pioglitazone on viability, proliferation, morphology, and differentiation in six GSC lines isolated from GBM patients. We also analyzed Pioglitazone-induced changes in transcriptional levels of Wnt/βcatenin related genes. Results showed that response to Pioglitazone was heterogeneous inducing an evident decrease of cell viability and proliferation only in a subset of GSC lines. We did not find any sign of cell differentiation neither observing cell morphology nor analyzing the expression of stemness and differentiation markers. Moreover, Wnt/βsignaling pathway was only mildly affected from a transcriptional point of view after Pioglitazone exposure.
Analysis of the Stability of the Riemann Problem for a Simplified Model in Magnetogasdynamics
Authors: Liu Yujin , Sun Wenhua
Published: May 2016

The generalized Riemann problem for a simplified model of one-dimensional ideal gas in magnetogasdynamics in a neighborhood of the origin(t>0)in the(x,t)plane is considered. According to the different cases of the corresponding Riemann solutions, we construct the perturbed solutions uniquely with the characteristic method. We find that, for some case, the contact discontinuity appears after perturbation while there is no contact discontinuity of the corresponding Riemann solution. For most cases, the Riemann solutions are stable and the perturbation can not affect the corresponding Riemann solutions. While, for some few cases, the forward (backward) rarefaction wave can be transformed into the forward (backward) shock wave which shows that the Riemann solutions are unstable under such local small perturbations of the Riemann initial data.
Characterization of Cellulose Synthesis in Plant Cells
Authors: Maleki Samaneh Sadat , Mohammadi Kourosh , Ji Kong-shu
Published: May 2016

Cellulose is the most significant structural component of plant cell wall. Cellulose, polysaccharide containing repeated unbranchedβ(1-4) D-glucose units, is synthesized at the plasma membrane by the cellulose synthase complex (CSC) from bacteria to plants. The CSC is involved in biosynthesis of cellulose microfibrils containing 18 cellulose synthase (CesA) proteins. Macrofibrils can be formed with side by side arrangement of microfibrils. In addition, beside CesA, various proteins like the KORRIGAN, sucrose synthase, cytoskeletal components, and COBRA-like proteins have been involved in cellulose biosynthesis. Understanding the mechanisms of cellulose biosynthesis is of great importance not only for improving wood production in economically important forest trees to mankind but also for plant development. This review article covers the current knowledge about the cellulose biosynthesis-related gene family.
Severe Cardiomyopathy after Huffing Dust-Off™
Authors: Cates Alexis L. , Cook Matthew D.
Published: May 2016

A 34-year-old man was found down in a parking lot after huffing fifteen cans of Dust-Off. Though lucid during the initial hospital evaluation, the patient experienced a generalized seizure followed by a torsades de pointes arrhythmia and was resuscitated. An echocardiogram revealed left and right ventricular dysfunction with an ejection fraction of 25%. This unique outcome of inhalant abuse has scarcely been reported in similar cases. The patient fully recovered and had a normal ejection fraction prior to discharge.
Resveratrol: A Potential Hippocampal Plasticity Enhancer
Authors: Dias Gisele Pereira , Cocks Graham , do Nascimento Bevilaqua Mário Cesar , Nardi Antonio Egidio , Thuret Sandrine
Published: May 2016

The search for molecules capable of restoring altered hippocampal plasticity in psychiatric and neurological conditions is one of the most important tasks of modern neuroscience. It is well established that neural plasticity, such as the ability of the postnatal hippocampus to continuously generate newly functional neurons throughout life, a process called adult hippocampal neurogenesis (AHN), can be modulated not only by pharmacological agents, physical exercise, and environmental enrichment, but also by “nutraceutical” agents. In this review we focus on resveratrol, a phenol and phytoalexin found in the skin of grapes and red berries, as well as in nuts. Resveratrol has been reported to have antioxidant and antitumor properties, but its effects as a neural plasticity inducer are still debated. The current review examines recent evidence implicating resveratrol in regulating hippocampal neural plasticity and in mitigating the effects of various disorders and diseases on this important brain structure. Overall, findings show that resveratrol can improve cognition and mood and enhance hippocampal plasticity and AHN; however, some studies report opposite effects, with resveratrol inhibiting aspects of AHN. Therefore, further investigation is needed to resolve these controversies before resveratrol can be established as a safe coadjuvant in preventing and treating neuropsychiatric conditions.
MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity
Authors: Chen Yi-Fen , Yang Cheng-Chieh , Kao Shou-Yen , Liu Chung-Ji , Lin Shu-Chun , Chang Kuo-Wei
Published: May 2016

miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo. Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872–86. ©2016 AACR.
Tissue Factor Induced by Epithelial–Mesenchymal Transition Triggers a Procoagulant State That Drives Metastasis of Circulating Tumor Cells
Authors: Bourcy Morgane , Suarez-Carmona Meggy , Lambert Justine , Francart Marie-Emilie , Schroeder Hélène , Delierneux Céline , Skrypek Nicolas , Thompson Erik W. , Jérusalem Guy , Berx Geert , Thiry Marc , Blacher Silvia , Hollier Brett G. , Noël Agnès , Oury Cécile , Polette Myriam , Gilles Christine
Published: May 2016

Epithelial–mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTCs with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related procoagulant properties in the blood. TF blockade by antibody or shRNA diminished the procoagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties, and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT–TF regulatory axis that triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTCs. Cancer Res; 76(14); 4270–82. ©2016 AACR.
The Mitogen-Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor Dasatinib in Thyroid Cancer
Authors: Beadnell Thomas C. , Mishall Katie M. , Zhou Qiong , Riffert Stephen M. , Wuensch Kelsey E. , Kessler Brittelle E. , Corpuz Maia L. , Jing Xia , Kim Jihye , Wang Guoliang , Tan Aik Choon , Schweppe Rebecca E.
Published: May 2016

Advanced stages of papillary and anaplastic thyroid cancer represent a highly aggressive subset, in which there are currently few effective therapies. We and others have recently demonstrated that c-SRC is a key mediator of growth, invasion, and metastasis, and therefore represents a promising therapeutic target in thyroid cancer. However, clinically, Src inhibitor efficacy has been limited, and therefore further insights are needed to define resistance mechanisms and determine rational combination therapies. We have generated four thyroid cancer cell lines with a greater than 30-fold increase in acquired resistance to the Src inhibitor dasatinib. Upon acquisition of dasatinib resistance, the two RAS-mutant cell lines acquired the c-SRC gatekeeper mutation (T341M), whereas the two BRAF-mutant cell lines did not. Accordingly, Src signaling was refractory to dasatinib treatment in the RAS-mutant dasatinib-resistant cell lines. Interestingly, activation of the MAPK pathway was increased in all four of the dasatinib-resistant cell lines, likely due to B-Raf and c-Raf dimerization. Furthermore, MAP2K1/MAP2K2 (MEK1/2) inhibition restored sensitivity in all four of the dasatinib-resistant cell lines, and overcame acquired resistance to dasatinib in the RAS-mutant Cal62 cell line, in vivo. Together, these studies demonstrate that acquisition of the c-SRC gatekeeper mutation and MAPK pathway signaling play important roles in promoting resistance to the Src inhibitor dasatinib. We further demonstrate that up-front combined inhibition with dasatinib and MEK1/2 or ERK1/2 inhibitors drives synergistic inhibition of growth and induction of apoptosis, indicating that combined inhibition may overcome mechanisms of survival in response to single-agent inhibition. Mol Cancer Ther; 15(8); 1952–63. ©2016 AACR.
High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic
Authors: Bessa Danielle S. , Macedo Delanie B. , Brito Vinicius N. , França Monica M. , Montenegro Luciana R. , Cunha-Silva Marina , Silveira Leticia G. , Hummel Tiago , Bergadá Ignacio , Braslavsky Debora , Abreu Ana Paula , Dauber Andrew , Mendonca Berenice B. , Kaiser Ursula B. , Latronico Ana Claudia
Published: May 2016

Background/Aims: Recently, loss-of-function mutations in the MKRN3 gene have been implicated in the etiology of familial central precocious puberty (CPP) in both sexes. We aimed to analyze the frequency of MKRN3 mutations in boys with CPP and to compare the clinical and hormonal features of boys with and without MKRN3 mutations. Methods: This was a retrospective review of clinical, hormonal and genetic features of 20 male patients with idiopathic CPP evaluated at an academic medical center. The entire coding regions of MKRN3, KISS1 and KISS1R genes were sequenced. Results: We studied 20 boys from 17 families with CPP. All of them had normal brain magnetic resonance imaging. Eight boys from 5 families harbored four distinct heterozygous MKRN3 mutations predicted to be deleterious for protein function, p.Ala162Glyfs*14, p.Arg213Glyfs*73, p.Arg328Cys and p.Arg365Ser. One boy carried a previously described KISS1-activating mutation (p.Pro74Ser). The frequency of MKRN3 mutations among these boys with idiopathic CPP was significantly higher than previously reported female data (40 vs. 6.4%, respectively, p < 0.001). Boys with MKRN3 mutations had typical clinical and hormonal features of CPP. Notably, they had later pubertal onset than boys without MKRN3 abnormalities (median age 8.2 vs. 7.0 years, respectively, p = 0.033). Conclusion: We demonstrated a high frequency of MKRN3 mutations in boys with CPP, previously classified as idiopathic, suggesting the importance of genetic analysis in this group. The boys with CPP due to MKRN3 mutations had classical features of CPP, but with puberty initiation at a borderline age.
Predicting Adverse Outcomes After Myocardial Infarction Among Patients With Diabetes Mellitus
Authors: Arnold Suzanne V. , Spertus John A. , Jones Philip G. , McGuire Darren K. , Lipska Kasia J. , Xu Yaping , Stolker Joshua M. , Goyal Abhinav , Kosiborod Mikhail
Published: May 2016

Background—

Although patients with diabetes mellitus experience high rates of adverse events after acute myocardial infarction (AMI), including death and recurrent ischemia, some diabetic patients are likely at low risk, whereas others are at high risk. We sought to develop prediction models to stratify risk after AMI in patients with diabetes mellitus.

Methods and Results—

We developed prediction models for long-term mortality and angina among 1613 patients with diabetes mellitus discharged alive after AMI from 24 US hospitals and then validated the models in a separate, multicenter registry of 786 patients with diabetes mellitus. Event rates in the derivation cohort were 27% for 5-year mortality and 27% for 1-year angina. Parsimonious prediction models demonstrated good discrimination (
c
-indices=0.78 and 0.69, respectively) and excellent calibration. Within the context of the predictors we estimated, the strongest predictors for mortality were higher creatinine, not working at the time of the AMI, older age, lower hemoglobin, left ventricular dysfunction, and chronic heart failure. The strongest predictors for angina were angina burden in the 4 weeks before the AMI, younger age, history of prior coronary bypass graft surgery, and non-white race. The lowest and highest deciles of predicted risk ranged from 4% to 80% for mortality and 12% to 59% for angina. The models also performed well in external validation (
c
-indices=0.78 and 0.73, respectively).

Conclusions—

We found a wide range of risk for adverse outcomes after AMI in diabetic patients. Predictive models can identify patients with diabetes mellitus for whom closer follow-up and aggressive secondary prevention strategies should be considered.
Smoking–Thrombolysis Relationship Depends on Ischemic Stroke Subtype
Authors: Tong Xu , Wang Chunjuan , Liao Xiaoling , Pan Yuesong , Yan Hongyi , Cao Yibin , Liu Liping , Zheng Huaguang , Zhao Xingquan , Wang Chunxue , Li Hao , Wang David , Wang Yilong , Wang Yongjun
Published: May 2016

Background and Purpose—

The relationship between smoking and the outcome in patients received thrombolysis is undetermined. The outcome could be influenced by different stroke subtypes. This study aimed to explore whether smoking had any impact on the outcome in patients with stroke of different subtypes who received intravenous thrombolysis.

Methods—

All patients who received intravenous thrombolysis within 4.5 hours after symptom onset from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) database were eligible to be entered into this analysis. Smokers were considered if they smoked at least 1 cigarette/d for >6 months before stroke. Ischemic stroke subtype was classified by using the Trial of Org 10172 in Acute Stroke Treatment criteria. Outcome measurements included post–intravenous thrombolysis symptomatic intracranial hemorrhage within 7 days, mortality, and functional independence at 90 days. The relationship between smoking and thrombolysis was analyzed by using univariate and multivariate logistic regression models.

Results—

Of 1118 patients enrolled, we identified 454 smokers and 664 nonsmokers. After stratifying for ischemic stroke subtypes, multivariate analysis revealed a significant relationship between smoking and functional independence in patients with noncardioembolism stroke subtypes (large artery atherosclerosis: odds ratio [OR], 1.452; 95% confidence interval [CI], 1.053–2.264; small artery occlusion: OR, 4.275; 95% CI, 1.098–16.649; other: OR, 3.120; 95% CI, 1.162–8.373). Furthermore, smoking was specially related to lower rates of symptomatic intracranial hemorrhage (OR, 0.316; 95% CI, 0.120–0.832) and mortality (OR, 0.272; 95% CI, 0.128–0.577) in patients with large artery atherosclerosis subtype.

Conclusions—

In patients treated with intravenous thrombolysis, smoking could be related to a better chance of functional independence if their subtype of stroke was noncardioembolic, and a lower risk of symptomatic intracranial hemorrhage and mortality in those with large artery atherosclerosis.