bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscular strengthening activity patterns and metabolic health risk among US adults*
Authors: CHURILLA James R. , MAGYARI Peter M. , FORD Earl S. , FITZHUGH Eugene C. , JOHNSON Tammie M.
Published: November 2011

Background:  Many studies have examined the relationship between physical activity and metabolic disorders. However, few have focused on specific associations between these disorders and muscular strengthening activity (MSA) patterns. The aim of the present study was to examine the association(s) for each metabolic syndrome criterion and MSA patterns.

Methods:  The study sample (n = 5618) consisted of adults ≥20 years of age who participated in the 1999–2004 National Health and Nutrition Examination Survey. Cut‐off points for metabolic syndrome criteria were derived from the American Heart Association/National Heart, Lung, and Blood Institute definition. The aggregate of data on weight lifting, push‐ups, and sit‐ups was used to establish patterns of MSA. Participants reporting ≥2 days/week MSA were coded as meeting current US MSA guidelines.

Results:  Following adjustments, participants reporting ≥2 days/week MSA were found to be 28% (OR 0.72; 95% CI 0.62, 0.83) less likely to have dyslipidemia, 29% (OR 0.71; 95% CI 0.54, 0.93) less likely to have impaired fasting glucose, 19% (OR 0.81; 95% CI 0.65, 0.99) less likely to have prehypertension, and 43% (OR 0.57; 95% CI 0.46, 0.72) less likely to have augmented waist circumference compared with those reporting engaging in no MSA. No association was found for hypertension and MSA.

Conclusion:  Engaging in ≥2 days/week MSA as part of an overall physical activity regimen may be prudent in preserving metabolic health. These findings strengthen the relationship between MSA and metabolic health; thus, clinicians should include MSA when discussing lifestyle approaches to better health.
Simulating switchgrass biomass production across ecoregions using the DAYCENT model
Authors: Lee Juhwan , Pedroso Gabriel , Linquist Bruce A. , Putnam Daniel , van Kessel Chris , Six Johan
Published: November 2011

The production potential of switchgrass (Panicum virgatum L.) has not been estimated in a Mediterranean climate on a regional basis and its economic and environmental contribution as a biofuel crop remains unknown. The objectives of the study were to calibrate and validate a biogeochemical model, DAYCENT, and to predict the biomass yield potential of switchgrass across the Central Valley of California. Six common cultivars were calibrated using published data across the US and validated with data generated from four field trials in California (2007–2009). After calibration, the modeled range of yields across the cultivars and various management practices in the US (excluding California) was 2.4–41.2 Mg ha−1 yr−1, generally compatible with the observed yield range of 1.3–33.7 Mg ha−1 yr−1. Overall, the model was successfully validated in California; the model explained 66–90% of observed yield variation in 2007–2009. The range of modeled yields was 2.0–41.4 Mg ha−1 yr−1, which corresponded to the observed range of 1.3–41.1 Mg ha−1 yr−1. The response to N fertilizer and harvest frequency on yields were also reasonably validated. The model estimated that Alamo (21–23 Mg ha−1 yr−1) and Kanlow (22–24 Mg ha−1 yr−1) had greatest yield potential during the years after establishment. The effects of soil texture on modeled yields tended to be consistent for all cultivars, but there were distinct climatic (e.g., annual mean maximum temperature) controls among the cultivars. Our modeled results suggest that early stand maintenance of irrigated switchgrass is strongly dependent on available soil N; estimated yields increased by 1.6–5.5 Mg ha−1 yr−1 when residual soil mineral N was sufficient for optimal re‐growth. Therefore, management options of switchgrass for regional biomass production should be ecotype‐specific and ensure available soil N maintenance.
Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model
Authors: Sghendo Lino , Mifsud Janet
Published: November 2011

Objectives

Serotonin is a monoamine neurotransmitter that is widely distributed in the body and plays an important role in a variety of psychological and other body functions such as mood, sexual desire and function, appetite, sleep, memory and learning, temperature regulation and social behaviour. This review will assess the use of fluoxetine, one of the most commonly used selective serotonin reuptake inhibitors, as a model for understanding the molecular pharmacology of the serotoninergic system.

Key findings

Seven serotonin receptor families have been discovered to date. All serotonin receptors, except 5-HT3, are G-protein coupled, seven transmembrane receptors that activate an intracellular second messenger cascade. The 5-HT3 receptor is a ligand-gated ion channel. Furthermore, 5-HT1A receptors are known as autoreceptors since their stimulation inhibits the release serotonin in nerve terminals. A transporter protein found in the plasma membrane of serotonergic neurones is responsible for the reuptake of this neurotransmitter. Selective serotonin reuptake inhibitors, such as fluoxetine, act primarily at the serotonin transporter protein and have limited, if any, reaction with other neurotransmitter systems. Selective serotonin reuptake inhibitors appear to bind with the serotonin transporter with different rates of occupancy, duration and potency.

The following review focuses on the interaction of serotonin with this membrane transporter in the body and assesses the use of fluoxetine as a reference drug in the understanding of this interaction.
The effect of propolis on CCL5 and IFN-γ expression by peripheral blood mononuclear cells from leishmaniasis patients
Authors: Amarante Marla Karine , Watanabe Maria Angélica Ehara , Conchon-Costa Ivete , Fiori Leandra Lopes , Oda Julie Massayo Maeda , Búfalo Michelle Cristiane , Sforcin José Maurício
Published: November 2011

Objectives

Mucocutaneous leishmaniasis is associated with a strong Th1 immune response to Leishmania, which modulates chemokines and their receptors expression, affecting their migratory capacity. There are no antileishmanial vaccines available and chemotherapy still relies on the potentially toxic pentavalent antimonials. Propolis is a bee product with immunomodulatory and antiparasite activities, and researchers have been attracted to its potential for the development of new drugs. This work investigated the effects of propolis on CCL5 and IFN-γ expression by peripheral blood mononuclear cells (PBMC) in order to evaluate a possible immunomodulatory action of propolis in patients with leishmaniasis compared to healthy control subjects.

Methods

PBMC were incubated in the absence or presence of propolis and the evaluation of a possible cytotoxicity of propolis was carried out using MTT assay. The expression level of CCL5 and IFN-γ was determined by real-time PCR.

Key findings

Our data indicated that propolis modulates the immune response of leishmaniasis patients in vitro, affecting CCL5 and IFN-γ expression by PBMC.

Conclusions

Data suggested that propolis drives an anti-inflammatory response depending on concentration. Although propolis is a potential source of new and selective drugs for the treatment of leishmaniasis, its usefulness in the therapeutics should be further investigated.
Susceptibility of glucocorticoids to colonic metabolism and pharmacologic intervention in the metabolism: implication for therapeutic activity of colon-specific glucocorticoid 21-sulfate sodium at the target site
Authors: Kong Hyesik , Lee Yonghyun , Kim Hyunjeong , Hong Sungchae , Kim Dae-Duk , Yoon Jeong-Hyun , Jung Yunjin , Kim Young Mi
Published: November 2011

Objectives

The systemic side effects of glucocorticoids have prevented their long-term use for treatment of inflammatory bowel disease. Colon-specific delivery of glucocorticoids has been adopted as a strategy to circumvent the toxicological trouble. Glucocorticoids delivered to the large intestine might undergo metabolisms by colonic microflora, which should affect therapeutic availability at the target site. It was investigated whether the susceptibility of glucocorticoids to the colonic metabolisms and pharmacologic intervention in the metabolism could modulate the therapeutic availability of colon-targeted glucocorticoids.

Methods

Various glucocorticoids and their derivatives, glucocorticoid 21-sulfate sodium compounds, were incubated in the cecal contents in the presence or absence of reduction inhibitors and the change in the levels of the drugs was monitored.

Key findings

The accumulation profiles of the corresponding glucocorticoids liberated from glucocorticoid 21-sulfate sodium compounds vary, depending on the metabolic susceptibility of glucocorticoids. Reduction inhibitors prevented the cecal metabolisms of glucocorticoids, which was most prominent for prednisolone (PD) and methylprednisolone (MP). Moreover, reduction inhibitors increased the accumulated amount of MP and PD released from PD- and MP-21-sulfate sodium in the cecal contents.

Conclusions

Our data provide information useful for selection of a glucocorticoid and a pharmacologic strategy for the design of an efficient colon-specific glucocorticoid prodrug.
Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration
Authors: Carosio Roberta , Pistoia Vito , Orienti Isabella , Formelli Franca , Cavadini Elena , Mangraviti Salvatore , Montaldo Paolo G , Ognio Emanuela , Emionite Laura , Zuccari Guendalina
Published: November 2011

Objectives

The major limitation to successful chemotherapy of neuroblastoma (NB) is the toxicity and the poor bioavailability of traditional drugs.

Methods

We synthesised an amphiphilic dextrin derivative (DX-OL) able to host fenretinide (4-HPR) by complexation. In this study, we have investigated the effects of 4-HPR-loaded amphipilic dextrin (DX-OL/4-HPR) in comparison with 4-HPR alone both in vitro on human NB cells and in vivo in pseudometastatic NB models. The haemolysis assay was used as a measure of the potential damage caused by the pharmaceutical formulation in vivo. Pharmacokinetic experiments were performed to assess drug plasma levels in mice treated with free or complexed 4-HPR.

Key findings

DX-OL/4-HPR exerted a more potent cytotoxic activity on NB cells. Complexed 4-HPR significantly increased the proportion of sub-G1 cells with respect to free 4-HPR. Dextrin derivatives showed no haemolytic activity, indicating their suitability for parenteral administration. DX-OL/4-HPR increased the lifespan and the long-term survival of treated mice over controls. The analysis of drug plasma levels indicates that the complexed drug has a higher AUC due to a reduced clearance from the blood.

Conclusions

Our data suggest that DX-OL/4-HPR is an injectable formulation that is able to improve drug aqueous solubility and bioavailability.
Metabolism of cryptolepine and 2-fluorocryptolepine by aldehyde oxidase
Authors: Stell J Godfrey P , Wheelhouse Richard T , Wright Colin W
Published: November 2011

Objectives

To investigate the metabolism of cryptolepine and some cryptolepine analogues by aldehyde oxidase, and to assess the implications of the results on the potential of cryptolepine analogues as antimalarial agents.

Methods

The products resulting from the oxidation of cryptolepine and 2-fluorocryptolepine by a rabbit liver preparation of aldehyde oxidase were isolated and identified using chromatographic and spectroscopic techniques. The antiplasmodial activity of cryptolepine-11-one was assessed against Plasmodium falciparum using the parasite lactate dehydrogenase assay.

Key findings

Cryptolepine was oxidized by aldehyde oxidase give cryptolepine-11-one. Although 2-fluorocryptolepine was found to have less affinity for the enzyme than cryptolepine, it was a better substrate for aldehyde oxidase than the parent compound. In contrast, quindoline, the 11-chloro- , 2,7-dibromo- and 2-methoxy analogues of cryptolepine were not readily oxidized. Cryptolepine-11-one was found to be inactive against P. falciparum in vitro raising the possibility that the effectiveness of cryptolepine as an antimalarial, may be compromised by metabolism to an inactive metabolite by liver aldehyde oxidase.

Conclusions

Cryptolepine and 2-fluorocryptolepine are substrates for aldehyde oxidase. This may have implications for the design and development of cryptolepine analogues as antimalarial agents.
On the Scaling of Pool Boiling Heat Flux With Gravity and Heater Size
Authors: Raj Rishi , Kim Jungho , McQuillen John
Published: November 2011

A framework for scaling pool boiling heat flux is developed using data from various heater sizes over a range of gravity levels. Boiling is buoyancy dominated for large heaters and/or high gravity conditions and the heat flux is heater size independent. The power law coefficient for gravity is a function of wall temperature. As the heater size or gravity level is reduced, a sharp transition in the heat flux is observed at a threshold value of Lh/Lc = 2.1. Below this threshold value, boiling is surface tension dominated and the dependence on gravity is smaller. The gravity scaling parameter for the heat flux in the buoyancy dominated boiling regime developed in the previous work is updated to account for subcooling effect. Based on this scaling parameter and the transition criteria, a methodology for predicting heat flux in the surface tension dominated boiling regime, typically observed under low-gravity conditions, is developed. Given the heat flux at a reference gravity level and heater size, the current framework allows the prediction of heat flux at any other gravity level and/or heater size under similar experimental conditions. The prediction is validated using data at over a range of subcoolings (11 °C ≤ ΔTsub ≤ 32.6 °C), heater sizes (2.1 mm ≤ Lh ≤ 7 mm), and dissolved gas concentrations (3 ppm ≤ cg ≤ 3500 ppm). The prediction errors are significantly smaller than those from correlations currently available in the literature.
Boundary Control of Temperature Distribution in a Spherical Shell With Spatially Varying Parameters
Authors: Rastgoftar Hossein , Eghtesad Mohammad , Khayatian Alireza
Published: November 2011

This paper presents a solution to the control (stabilization) problem of temperature distribution in spherical shells with spatially varying properties. The desired temperature distribution satisfies the steady-state heat conduction equation. For the spherical shell under consideration, it is assumed that material properties such as thermal conductivity, density, and specific heat capacity may vary in radial, polar, and azimuthal directions of the spherical shell; the governing heat conduction equation of the shell is a second-order partial differential equation. Using Lyapunov’s theorem, it is shown how to obtain boundary heat flux required for producing a desired steady-state distribution of the temperature. Finally, numerical simulation is provided to verify the effectiveness of the proposed method such that by applying the boundary transient heat flux, in-domain distributed temperature converges to its desired steady-state temperature.
The Origin of OB Runaway Stars
Authors: Fujii Michiko S. , Zwart Simon Portegies
Published: November 2011

Most of the unusually fast, young stars in our Galaxy are produced in three-body encounters within dense clusters of stars.
Imaging of
Plasmodium
Liver Stages to Drive Next-Generation Antimalarial Drug Discovery
Authors: Meister Stephan , Plouffe David M. , Kuhen Kelli L. , Bonamy Ghislain M. C. , Wu Tao , Barnes S. Whitney , Bopp Selina E. , Borboa Rachel , Bright A. Taylor , Che Jianwei , Cohen Steve , Dharia Neekesh V. , Gagaring Kerstin , Gettayacamin Montip , Gordon Perry , Groessl Todd , Kato Nobutaka , Lee Marcus C. S. , McNamara Case W. , Fidock David A. , Nagle Advait , Nam Tae-gyu , Richmond Wendy , Roland Jason , Rottmann Matthias , Zhou Bin , Froissard Patrick , Glynne Richard J. , Mazier Dominique , Sattabongkot Jetsumon , Schultz Peter G. , Tuntland Tove , Walker John R. , Zhou Yingyao , Chatterjee Arnab , Diagana Thierry T. , Winzeler Elizabeth A.
Published: November 2011

Imidazolopiperazine compounds inhibit liver-stage malaria parasites with one oral dose in mice.
International disease monitoring, July to September 2011
Authors: Roberts H. , Lopez M.
Published: November 2011

African swine fever continues to spread in western Russia

Deboned and matured beef imports to the EU from Paraguay suspended due to foot‐and‐mouth disease

Spread of a new clade of highly pathogenic avian influenza in south‐east Asia

Rabies case in France in an illegally imported pet dog

Re‐emergence of West Nile fever in southern Europe

These are among matters discussed in the international disease monitoring report for July to September 2011, prepared by Defra's Animal Health and Veterinary Laboratories Agency
KINEMATICALLY BLOCKED CURVATON
Authors: LEE LU-YUN , LIN CHIA-MIN , CHEN CHIAN-SHU
Published: November 2011

In this paper, we investigate the idea that the decay of a curvaton is kinematically blocked and show that the coupling constant for curvaton decay can be as large as [Formula: see text]. We also find in this case the lower bound of the Hubble parameter at horizon exit from big bang nucleosynthesis (BBN) is H* ≳ 7.2 × 10-9M P ~ 1010 GeV . Similar to conventional curvaton scenario, the nonlinear parameter can be as large as fNL = 100.
SPECTRUM OF GRAVITATIONAL WAVES IN KREIN SPACE QUANTIZATION
Authors: MOHSENZADEH M. , SOJASI A. , YUSOFI E.
Published: November 2011

The main goal of this paper is to derive the primordial power spectrum for the scalar perturbations generated as a result of quantum fluctuations during an inflationary period by an alternative approach of field quantization.1–3 Formulas are derived for the gravitational waves, special cases of which include power law inflation and inflation in the slow roll approximation, in Krein space quantization.
NEUTRINO PHYSICS: A STATUS REPORT
Authors: BRUGNERA RICCARDO
Published: November 2011

In this paper we summarize the status of neutrino oscillations and neutrino direct mass searches from an experimentalist point of view. Emphasis is posed in the latest results and in the future perspectives.
Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation
Authors: Evans Zachary P. , Palanisamy Arun P. , Sutter Alton G. , Ellett Justin D. , Ramshesh Venkat K. , Attaway Hubert , Schmidt Michael G. , Schnellmann Rick G. , Chavin Kenneth D.
Published: November 2011

Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation.
Metabolic development in the liver and the implications of the n-3 fatty acid supply
Authors: Novak Elizabeth M. , Keller Bernd O. , Innis Sheila M.
Published: November 2011

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine ( P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways.
Mechanism of loss of consciousness during vascular neck restraint
Authors: Mitchell Jamie R. , Roach Dan E. , Tyberg John V. , Belenkie Israel , Sheldon Robert S.
Published: November 2011

Vascular neck restraint (VNR) is a technique that police officers may employ to control combative individuals. As the mechanism of unconsciousness is not completely understood, we tested the hypothesis that VNR simply compresses the carotid arteries, thereby decreasing middle cerebral artery blood flow. Twenty-four healthy police officers (age 35 ± 4 yr) were studied. Heart rate (HR), arterial pressure, rate of change of pressure (dP/d t), and stroke volume (SV) were measured using infrared finger photoplethysmography. Bilateral mean middle cerebral artery flow velocity (MCAVmean) was measured by using transcranial Doppler ultrasound. Neck pressure was measured using flat, fluid-filled balloon transducers positioned over both carotid bifurcations. To detect ocular fixation, subjects were asked to focus on a pen that was moved from side to side. VNR was released 1–2 s after ocular fixation. Ocular fixation occurred in 16 subjects [time 9.5 ± 0.4 (SE) s]. Pressures over the right (R) and left (L) carotid arteries were 257 ± 22 and 146 ± 18 mmHg, respectively. VNR decreased MCAVmean (R 45 ± 3 to 8 ± 4 cm/s; L 53 ± 2 to 10 ± 3 cm/s) and SV (92 ± 4 to 75 ± 4 ml; P < 0.001). Mean arterial pressure (MAP), dP/d t, and HR did not change significantly. We conclude that the most important mechanism in loss of consciousness was decreased cerebral blood flow caused by carotid artery compression. The small decrease in CO (9.6 to 7.5 l/min) observed would not seem to be important as there was no change in MAP. In addition, with no significant change in HR, ventricular contractility, or MAP, the carotid sinus baroreceptor reflex appears to contribute little to the response to VNR.
ATM-Mediated DNA Damage Signals Mediate Immune Escape through Integrin-αvβ3–Dependent Mechanisms
Authors: Jinushi Masahisa , Chiba Shigeki , Baghdadi Muhammad , Kinoshita Ichiro , Dosaka-Akita Hirotoshi , Ito Koyu , Yoshiyama Hironori , Yagita Hideo , Uede Toshimitsu , Takaoka Akinori
Published: November 2011

Although the tumor microenvironment plays a critical role in tumor progression and metastasis, the relationship between chemotherapy resistance and modulation of the tumor microenvironment remains unclear. Here, we report a novel mechanism showing how constitutive DNA damage signals in therapy-resistant tumor cells suppress antitumor immunity in an integrin-αvβ3–dependent manner. Integrin-αvβ3 was upregulated on various therapy-resistant tumor cells through chronic activation of ATM/Chk2-and NFκB-mediated pathways. Inhibiting tumor-specific expression of integrin-αvβ3 improved therapeutic responses to anticancer drugs by stimulating endogenous host immune systems. Mechanistic investigations revealed that tumor-specific integrin-αvβ3 expression targeted dendritic cells, facilitating their ability to phagocytose viable therapy-resistant tumor cells and thereby impaired their ability to cross-prime antigen-specific T lymphocytes. Together, our results clarify the detrimental effects of constitutive DNA damage signals to chemosensitivity and antitumor immunity. Furthermore, these findings suggest that integrin-αvβ3 targeting may benefit patients' refractory to current anticancer regimens by defeating DNA damage signaling-induced immune escape. Cancer Res; 72(1); 56–65. ©2011 AACR.
EpCAM/CD3-Bispecific T-cell Engaging Antibody MT110 Eliminates Primary Human Pancreatic Cancer Stem Cells
Authors: Cioffi Michele , Dorado Jorge , Baeuerle Patrick A. , Heeschen Christopher
Published: November 2011

Purpose: Tumor-initiating cells with stem-like properties, also termed cancer stem cells (CSC), have been shown to sustain tumor growth as well as metastasis and are highly resistant to chemotherapy. Because pancreatic CSCs have been isolated on the basis of EpCAM expression, we investigated whether a targeted immunotherapy to EpCAM using the bispecific T-cell–engaging antibody MT110 is capable of eradicating CSCs.

Experimental Design: We studied in vitro and in vivo the effects of MT110 on CSCs using both established cell lines as well as primary cells of human pancreatic cancer.

Results: Although established cell lines were more responsive to MT110-engaged T cells, also primary cells showed a time- and dose-dependent response to treatment with the bispecific antibody. In addition, the population of highly tumorigenic CSCs was efficiently targeted by the EpCAM/CD3-bispecific antibody MT110 in vitro and in vivo using a mouse model of established primary pancreatic cancer. Pancreatic cancer cells derived from metastases were slightly more resistant to MT110 treatment on the basis of in vivo tumorigenicity studies. This appeared to be related to a higher frequency of an EpCAM-negative subpopulation of CSCs.

Conclusions: Cytotoxic T cells can be effectively redirected against primary human pancreatic cancer cells by T-cell–engaging BiTE antibody MT110 including a subpopulation of highly tumorigenic CSCs. Clin Cancer Res; 18(2); 465–74. ©2011 AACR.
Association of Testosterone Levels With Endothelial Function in Men
Authors: Empen Klaus , Lorbeer Roberto , Dörr Marcus , Haring Robin , Nauck Matthias , Gläser Sven , Krebs Alexander , Reffelmann Thorsten , Ewert Ralf , Völzke Henry , Wallaschofski Henri , Felix Stephan B.
Published: November 2011

Objective—

Because population-based data are lacking, we assessed the cross-sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania.

Methods and Results—

Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04–1.63;
P
=0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06–1.76;
P
=0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD.

Conclusion—

Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men.
Transforming Growth Factor-β–Induced Endothelial-to-Mesenchymal Transition Is Partly Mediated by MicroRNA-21
Authors: Kumarswamy Regalla , Volkmann Ingo , Jazbutyte Virginija , Dangwal Seema , Park Da-Hee , Thum Thomas
Published: November 2011

Objective—

MicroRNAs are a class of small ribonucleotides regulating gene/protein targets by transcript degradation or translational inhibition. Transforming growth factor-β (TGF-β) is involved in cardiac fibrosis partly by stimulation of endothelial-to-mesenchymal transition (EndMT). Here, we investigated whether microRNA (miR)-21, a microRNA enriched in fibroblasts and involved in general fibrosis, has a role in cardiac EndMT.

Methods and Results—

TGF-β treatment of endothelial cells significantly increased miR-21 expression and induced EndMT characterized by suppression of endothelial and increase of fibroblast markers. Overexpression of miR-21 alone also stimulated EndMT. Importantly, miR-21 blockade by transfection of specific microRNA inhibitors partly prevented TGF-β-induced EndMT. Mechanistically, miR-21 silenced phosphatase and tensin homolog in endothelial cells, resulting in activation of the Akt-pathway. Akt inhibition partly restored TGF-β-mediated loss of endothelial markers during EndMT. In vivo, pressure overload of the left ventricle led to increased expression of miR-21 in sorted cardiac endothelial cells, which displayed molecular and phenotypic signs of EndMT. This was attenuated by treatment of mice subjected to left ventricular pressure overload with an antagomir against miR-21.

Conclusion—

TGF-β-mediated EndMT is regulated at least in part by miR-21 via the phosphatase and tensin homolog/Akt pathway. In vivo, antifibrotic effects of miR-21 antagonism are partly mediated by blocking EndMT under stress conditions.
Inhibition of MicroRNA-29 Enhances Elastin Levels in Cells Haploinsufficient for Elastin and in Bioengineered Vessels—Brief Report
Authors: Zhang Pei , Huang Angela , Ferruzzi Jacopo , Mecham Robert P. , Starcher Barry C. , Tellides George , Humphrey Jay D. , Giordano Frank J. , Niklason Laura E. , Sessa William C.
Published: November 2011

Objective—

The goal of this study was to determine whether antagonizing microRNA (miR)-29 enhances elastin (ELN) levels in cells and tissues lacking ELN.

Methods and Results—

miR-29 mimics reduced ELN levels in fibroblasts and smooth muscle cells, whereas miR-29 inhibition increased ELN levels. Antagonism of miR-29 also increased ELN levels in cells from patients haploinsufficient for ELN and in bioengineered human vessels.

Conclusion—

miR-29 antagonism may promote increased ELN levels during conditions of ELN deficiencies.
NADPH Oxidase 4 Mediates Monocyte Priming and Accelerated Chemotaxis Induced by Metabolic Stress
Authors: Ullevig Sarah , Zhao Qingwei , Lee Chi Fung , Seok Kim Hong , Zamora Debora , Asmis Reto
Published: November 2011

Objective—

Metabolic disorders increase monocyte chemoattractant protein-1 (MCP-1)-induced monocyte chemotaxis in mice. The goal of this study was to determine the molecular mechanisms responsible for the enhanced responsiveness of monocytes to chemoattractants induced by metabolic stress.

Methods and Results—

Chronic exposure of monocytes to diabetic conditions induced by human LDL plus high D-glucose concentrations (LDL+HG) promoted NADPH Oxidase 4 (Nox4) expression, increased intracellular H
2
O
2
formation, stimulated protein
S
-glutathionylation, and increased chemotaxis in response to MCP-1, platelet-derived growth factor B, and RANTES. Both H
2
O
2
added exogenously and overexpression of Nox4 mimicked LDL+HG-induced monocyte priming, whereas Nox4 knockdown protected monocytes against metabolic stress-induced priming and accelerated chemotaxis. Exposure of monocytes to LDL+HG promoted the
S
-glutathionylation of actin, decreased the F-actin/G-actin ratio, and increased actin remodeling in response to MCP-1. Preventing LDL+HG-induced protein
S
-glutathionylation by overexpressing glutaredoxin 1 prevented monocyte priming and normalized monocyte chemotaxis in response to MCP-1. Induction of hypercholesterolemia and hyperglycemia in C57BL/6 mice promoted Nox4 expression and protein
S
-glutathionylation in macrophages, and increased macrophage recruitment into MCP-1–loaded Matrigel plugs implanted subcutaneous in these mice.

Conclusion—

By increasing actin-
S
-glutathionylation and remodeling, metabolic stress primes monocytes for chemoattractant-induced transmigration and recruitment to sites of vascular injury. This Nox4-dependent process provides a novel mechanism through which metabolic disorders promote atherogenesis.
Calpains Contribute to Vascular Repair in Rapidly Progressive Form of Glomerulonephritis: Potential Role of Their Externalization
Authors: Letavernier Béatrice , Zafrani Lara , Nassar Dany , Perez Joëlle , Levi Charlène , Bellocq Agnès , Mesnard Laurent , Sachon Emmanuelle , Haymann Jean-Philippe , Aractingi Selim , Faussat Anne-Marie , Baud Laurent , Letavernier Emmanuel
Published: November 2011

Objective—

Calpains, calcium-activated proteases, mediate the angiogenic signals of vascular endothelial growth factor. However, their involvement in vascular repair has not been investigated and the underlying mechanisms remain to be fully elucidated.

Methods and Results—

A rapidly progressive form of glomerulonephritis in wild type and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor, was studied. Calpastatin transgene expression prevented the repair of peritubular capillaries and the recovery of renal function, limiting mouse survival. In vitro analysis detected a significant reduction of both intracellular and extracellular calpain activities in transgene expressing cells, whereas Western blotting revealed that proangiogenic factors vascular endothelial growth factor and norepinephrine increased calpain exteriorization. In vitro, extracellular calpains increased endothelial cell proliferation, migration and capillary tube formation. In vivo, delivery of nonpermeable extracellular calpastatin was sufficient to blunt angiogenesis and vascular repair. Endothelial cell response to extracellular calpains was associated with fibronectin cleavage, generating fibronectin fragments with proangiogenic capacity. In vivo, fibronectin cleavage was limited in the kidney of calpastatin transgenic mice with nephritis.

Conclusion—

This study demonstrates that externalized calpains participate in angiogenesis and vascular repair, partly by promoting fibronectin cleavage and thereby amplifying vascular endothelial growth factor efficiency. Thus, manipulation of calpain externalization may have therapeutic implications to control angiogenesis.
The Cox-Maze Procedure for Lone Atrial Fibrillation
Authors: Weimar Timo , Schena Stefano , Bailey Marci S. , Maniar Hersh S. , Schuessler Richard B. , Cox James L. , Damiano Ralph J.
Published: November 2011

Background—

The Cox-Maze procedure (CMP) has achieved high success rates in the therapy of atrial fibrillation (AF) while becoming progressively less invasive. This report evaluates our experience with the CMP in the treatment of lone AF over 2 decades and compares the original cut-and-sew CMP-III to the ablation-assisted CMP-IV, which uses bipolar radiofrequency and cryoenergy to create the original lesion pattern.

Methods and Results—

Data were collected prospectively on 212 consecutive patients (mean age, 53.5±10.4 years; 78% male) who underwent a stand-alone CMP from 1992 through 2010. The median duration of preoperative AF was 6 (interquartile range, 2.9–11.5) years, with 48% paroxysmal and 52% persistent or long-standing persistent AF. Univariate analysis with preoperative and perioperative variables used as covariates for the CMP-III (n=112) and the CMP-IV (n=100) was performed. Overall, 30-day mortality was 1.4%, with no intraoperative deaths. Freedom from AF was 93%, and freedom from AF off antiarrhythmics was 82%, at a mean follow-up time of 3.6±3.1 years. Freedom from symptomatic AF at 10 years was 85%. Only 1 late stroke occurred, with 80% of patients not receiving anticoagulation therapy. The less invasive CMP-IV had significantly shorter cross-clamp times (41±13 versus 92±26 minutes;
P
<0.001) while achieving high success rates, with 90% freedom from AF and 84% freedom from AF off antiarrhythmics at 2 years.

Conclusions—

The CMP, although simplified and shortened by alternative energy sources, has excellent results, even with improved follow-up and stricter definition of failure.
Circadian Dependence of Infarct Size and Left Ventricular Function After ST Elevation Myocardial Infarction
Authors: Reiter Ronald , Swingen Cory , Moore Luke , Henry Timothy D. , Traverse Jay H.
Published: November 2011

Rationale:

In rodents, infarct size after ischemia/reperfusion exhibits a circadian dependence on the time of coronary occlusion. It is not known if a similar circadian dependence of infarct size occurs in humans.

Objective:

To determine if humans exhibit a circadian dependence of infarct size in the setting of ST elevation myocardial infarction (STEMI).

Methods and Results:

A retrospective analysis of 1031 patients with STEMI referred for primary percutaneous coronary intervention with known ischemic times between 1 and 6 hours identified 165 patients with occluded arteries on presentation without evidence of preinfarction angina or collateral blood flow. Both ischemic duration and angiographic area at risk were not dependent on time of infarct onset. We observed that the extent of infarct size measured by creatine kinase release was significantly associated with time of day onset of infarction (
P
<0.0001). The greatest myocardial injury occurred at 1:00
am
onset of ischemia and 5:00
am
onset of reperfusion, with the peak creatine kinase measured at the peak of the curve being 82% higher than that recorded at the trough. Similarly, left ventricular ejection fraction measured within 2 days of infarction was also dependent on time of onset of STEMI with the absolute left ventricular ejection fraction at peak >7% higher than at trough (43% vs 51%;
P
<0.03). These findings were supported by a subgroup of patients (n=45) who underwent cardiac MRI measurements of infarct size and area-at-risk measurements.

Conclusions:

The results of this study demonstrate for the first time in humans that myocardial infarct size and left ventricular function after STEMI have a circadian dependence on the time of day onset of ischemia.
Atrophy of Spared Gray Matter Tissue Predicts Poorer Motor Recovery and Rehabilitation Response in Chronic Stroke
Authors: Gauthier Lynne V. , Taub Edward , Mark Victor W. , Barghi Ameen , Uswatte Gitendra
Published: November 2011

Background and Purpose—

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage.

Methods—

Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery.

Results—

Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy.

Conclusions—

Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.
An Evolutionary Perspective on Play, Performance, and Ritual
Authors: McConachie Bruce
Published: November 2011

What can neuroscience, evolutionary psychology, and cognitive linguistics tell us about the probable origins of play? What was the likely order of the emergence of play, performance, and ritual in evolutionary time? As new scientific discoveries challenge older traditions and truisms of scholarship in performance studies, these questions take on new urgency and reshape key definitions in the field.
From Event to Extreme Reality: The Aesthetic of Shock
Authors: Féral Josette
Published: November 2011

We live in an era where many directors and artists in all disciplines seek to move beyond representation by bringing reality onto the stage, by creating the event—in truth, by introducing the spectacular. Presenting exceptionally violent, extreme scenes onstage brings art out of its theatrical framework and offers an experience identical to that of a real event.
Acts of Presence: Performance, Mediation, Virtual Reality
Authors: Kaye Nick , Giannachi Gabriella
Published: November 2011

The Acts of Presence: Performing Presence CAVE Scenarios DVD-ROM accompanies this article. Presence is central to the operation of immersive virtual reality facilities. These VR technologies explore how phenomena of presence are performed, mediated, and experienced by individual participants, defining questions in computer science that can be advanced through performance theory, while offering new ways of thinking around liveness and mediation.
The Criminalization of Dissent: Protest Violence, Activist Performance, and the Curious Case of the VolxTheaterKarawane in Genoa
Authors: Boyle Michael Shane
Published: November 2011

The arrest of the activist performance collective the VolxTheaterKarawane concretely reveals the discourse of criminalization state authorities used to brutally suppress dissent at the 2001 G8 Summit in Genoa, Italy. It is one example of the increasingly common strategy of political elites who promote the perception of political protest as a criminal act, a misapprehension that has profound consequences for the future of democracy and dissent in late capitalism.
Explaining How Brain Stimulation Can Evoke Memories
Authors: Jacobs Joshua , Lega Bradley , Anderson Christopher
Published: November 2011

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the “high school-ness” of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.
The Prefrontal Cortex and Oculomotor Delayed Response: A Reconsideration of the “Mnemonic Scotoma”
Authors: Tsujimoto Satoshi , Postle Bradley R.
Published: November 2011

The concept of the “mnemonic scotoma,” a spatially circumscribed region of working memory impairment produced by unilateral lesions of the PFC, is central to the view that PFC is critical for the short-term retention of information. Presented here, however, are previously unpublished data that offer an alternative, nonmnemonic interpretation of this pattern of deficit. In their study, Wajima and Sawaguchi [Wajima, K., & Sawaguchi, T. The role of GABAergic inhibiton in suppressing perseverative responses in the monkey prefrontal cortex. Neuroscience Research, 50(Suppl. 1), P3–P317, 2004] applied the GABAA antagonist bicuculline methiodide unilaterally to the PFC of two monkeys while they performed an oculomotor delayed-response task. Consistent with previous studies, errors for the initial memory-guided saccade were markedly higher when the cued location fell into the region of the visual field affected by the infusion. These erroneous saccades tended to select an alternative target location (out of a possible 16) that had not been cued on that trial. By extending the analysis window, however, it was observed that the second, “corrective” saccade often acquired the location that had been cued on that trial. Further analysis of the erroneous initial saccades indicated that they tended to be directed to a location that had been relevant on the previous trial. Thus, the deficit was not one of “forgetting” the cued location. Rather, it was one of selecting between currently and previously relevant locations. These findings suggest a need for a reconsideration of the concept of the mnemonic scotoma, which in turn invites a reconsideration of functional interpretations of sustained neuronal activity in PFC.
Value Resonance and Value Framing Effects on Voting Intentions in Direct-Democratic Campaigns
Authors: Schemer Christian , Wirth Werner , Matthes Jörg
Published: November 2011

This study offers insights into how news media frames interact with existing value orientations in shaping voter preferences. It is assumed that a framing effect should be more pronounced when frames in the news resonate with people’s existing value predispositions. These assumptions were tested in a real-world setting of a political campaign dealing with the issue of naturalization of immigrants. Based on a data set in which the data of a two-wave panel survey were matched with content analytic data, the present research demonstrated frame-resonance effects for news reporting about the pro campaign. That is, framing the issue in terms of the notion that people should have the final say in naturalization procedures shaped voting preferences only for voters whose basic values of social order, tradition, and security (high authoritarians) were touched. In contrast, a main effect of the opponents’ framing in the news on voting preferences was found. Thus, the majority followed the framing of the opponents who put emphasis on a fair and pragmatic solution of the naturalization issue.