bluuebunny/crossref_metadata_2025 huggingface dataset:
Arf1 and Arf6 promote ventral actin structures formed by acute activation of protein kinase C and Src
Authors: Caviston Juliane P. , Cohen Lee Ann , Donaldson Julie G.
Published: June 2014

Arf proteins regulate membrane traffic and organelle structure. Although Arf6 is known to initiate actin‐based changes in cell surface architecture, Arf1 may also function at the plasma membrane. Here we show that acute activation of protein kinase C (PKC) induced by the phorbol ester PMA led to the formation of motile actin structures on the ventral surface of Beas‐2b cells, a lung bronchial epithelial cell line. Ventral actin structures also formed in PMA‐treated HeLa cells that had elevated levels of Arf activation. For both cell types, formation of the ventral actin structures was enhanced by expression of active forms of either Arf1 or Arf6 and by the expression of guanine nucleotide exchange factors that activate these Arfs. By contrast, formation of these structures was blocked by inhibitors of PKC and Src and required phosphatidylinositol 4, 5‐bisphosphate, Rac, Arf6, and Arf1. Furthermore, expression of ASAP1, an Arf1 GTPase activating protein (GAP) was more effective at inhibiting the ventral actin structures than was ACAP1, an Arf6 GAP. This study adds to the expanding role for Arf1 in the periphery and identifies a requirement for Arf1, a “Golgi Arf,” in the reorganization of the cortical actin cytoskeleton on ventral surfaces, against the substratum. Published 2014. This article is a U.S. Government work and is in the public domain in the USA
Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents
Authors: Ettari Roberta , Pinto Andrea , Tamborini Lucia , Angelo Ilenia C. , Grasso Silvana , Zappalà Maria , Capodicasa Natale , Yzeiraj Laura , Gruber Esther , Aminake Makoah N. , Pradel Gabriele , Schirmeister Tanja , De Micheli Carlo , Conti Paola
Published: June 2014

Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds.
Anticancer Ruthenium(III) Complex KP1019 Interferes with ATP‐Dependent Ca2+Translocation by Sarco‐Endoplasmic Reticulum Ca2+‐ATPase (SERCA)
Authors: Sadafi Fabrizio‐Zagros , Massai Lara , Bartolommei Gianluca , Moncelli Maria Rosa , Messori Luigi , Tadini‐Buoninsegni Francesco
Published: June 2014

Sarco‐endoplasmic reticulum Ca2+‐ATPase (SERCA), a P‐type ATPase that sustains Ca2+transport and plays a major role in intracellular Ca2+homeostasis, represents a therapeutic target for cancer therapy. Here, we investigated whether ruthenium‐based anticancer drugs, namely KP1019 (indazolium [trans‐tetrachlorobis(1H‐indazole)ruthenate(III)]), NAMI‐A (imidazolium [trans‐tetrachloro(1H‐imidazole)(S‐dimethylsulfoxide)ruthenate(III)]) and RAPTA‐C ([Ru(η6‐p‐cymene)dichloro(1,3,5‐triaza‐7‐phosphaadamantane)]), and cisplatin (cis‐diammineplatinum(II) dichloride) might act as inhibitors of SERCA. Charge displacement by SERCA adsorbed on a solid‐supported membrane was measured after ATP or Ca2+concentration jumps. Our results show that KP1019, in contrast to the other metal compounds, is able to interfere with ATP‐dependent translocation of Ca2+ions. An IC50value of 1 μMwas determined for inhibition of calcium translocation by KP1019. Conversely, it appears that KP1019 does not significantly affect Ca2+binding to the ATPase from the cytoplasmic side. Inhibition of SERCA at pharmacologically relevant concentrations may represent a crucial aspect in the overall pharmacological and toxicological profile of KP1019.
A computational fluid dynamics study on hemodynamics for different locations of the distal anastomosis of a bypass nearby a collateral vessel in the femoropopliteal area
Authors: Rivera J. , van der Graaf G.B. , Escudero J.R. , Bellmunt S. , van de Vosse F.
Published: June 2014

Revascularization of the femoropopliteal sector is often performed by the placement of a bypass. In this paper, we have studied the effects of hemodynamics on patency of the bypass for different positions of the distal anastomosis close to a collateral artery. Computational fluid dynamics (CFD) are used for this study. The cardiac cycle‐averaged wall shear stress and oscillation index (OSI) have been analyzed. Low and high OSI may increase the risk of intimal hyperplasia (IH), which may reduce bypass patency. From the CFD simulations, spots of low and high OSI are found within and near the entrance of the collateral artery, near the suture line, at the floor, toe, and heel. We regarded flow ratios of 20:80 and of 35:65. It is found that for the high flow ratio anastomosis located proximal to the collateral artery is clearly more advantageous. However for the low flow ratio anastomosis located distal to the collateral artery seems to be slightly more advantageous, the results are less conclusive. One of the studied flow geometries has been validated by in vitro experiments using a time resolved particle image velocimetry technique. Velocity fields from these experiments are in good agreement with the CFD results. Copyright © 2014 John Wiley & Sons, Ltd.
Fulfilling mutual nonrepudiation for cloud storage
Authors: Hwang Gwan‐Hwan , Huang Wei‐Sian , Peng Jenn‐Zjone , Lin Yu‐Wei
Published: June 2014

In this paper, we propose solution for obtaining mutual nonrepudiation between the user and service provider in cloud storage. One of the solutions for mutual nonrepudiation is based on logging attestations, which are signed messages. For supporting write‐serializability and read freshness of files, an intuitive solution is to have attestations be chain hashed. However, it is inefficient when files in an account can be accessed by multiple client devices interchangeably because client devices must keep all the attestations or there must exist a way to broadcast the last attestation to all the client devices. We propose a scheme that can guarantee mutual nonrepudiation between the user and service provider without requiring the client devices to exchange any messages, and each client device only has to store the last attestation it received. Concurrent accesses of files should be forbidden if all attestations need to be chained together with one chain. We propose to use multiple chains to provide concurrent file accesses in a single account. In addition, we also propose how to apply the hash tree to remove accumulated attestations. The results from related experiments demonstrate the feasibility of the proposed scheme. A service provider of cloud storage can use the proposed scheme to provide a mutual nonrepudiation guarantee in their service‐level agreement. Copyright © 2014 John Wiley & Sons, Ltd.
Dispersion of T1 and T2 Nuclear Magnetic Resonance Relaxation in Crude Oils
Authors: Chen Joseph J. , Hürlimann Martin , Paulsen Jeffrey , Freed Denise , Mandal Soumyajit , Song Yi‐Qiao
Published: June 2014

Crude oils, which are complex mixtures of hydrocarbons, can be characterized by nuclear magnetic resonace diffusion and relaxation methods to yield physical properties and chemical compositions. In particular, the field dependence, or dispersion, of T1 relaxation can be used to investigate the presence and dynamics of asphaltenes, the large molecules primarily responsible for the high viscosity in heavy crudes. However, the T2 relaxation dispersion of crude oils, which provides additional insight when measured alongside T1, has yet to be investigated systematically. Here we present the field dependence of T1‐T2 correlations of several crude oils with disparate densities. While asphaltene and resin‐containing crude oils exhibit significant T1 dispersion, minimal T2 dispersion is seen in all oils. This contrasting behavior between T1 and T2 cannot result from random molecular motions, and thus, we attribute our dispersion results to highly correlated molecular dynamics in asphaltene‐containing crude oils.
Palladium Nanoparticles Supported on Poly(N‐vinyl‐ imidazole‐co‐N‐vinylcaprolactam) as an Effective Recyclable Catalyst for the Suzuki Reaction
Authors: Selivanova Alexandra V. , Tyurin Vladimir S. , Beletskaya Irina P.
Published: June 2014

A recyclable and effective polymer‐immobilized ligandless palladium catalyst for the Suzuki reaction has been investigated. Palladium nanoparticles are formed in situ and stabilized by poly(N‐vinylimidazole‐co‐N‐vinylcaprolactam). A series of aryl bromides have been studied in the reaction with phenylboronic acid under mild conditions with water–alcohol systems as a solvent that complies with “Green Chemistry” demands. The catalyst can be recycled eight times without appreciable loss in activity and a low degree of palladium leaching. Kinetic studies reveal unusual behavior of the reaction; this can be explained on the basis of the observation of changes to the sizes of the particles during recycling, as determined by TEM results. The suggested mechanism of the reaction is in accordance with the concept of the role of leaching in the process.
High‐Power Lithium‐Ion Capacitor using LiMnBO3‐Nanobead Anode and Polyaniline‐Nanofiber Cathode with Excellent Cycle Life
Authors: Karthikeyan Kaliyappan , Amaresh Samuthirapandian , Lee Sol‐Nip , An Jae‐Yeon , Lee Yun‐Sung
Published: June 2014

LiMnBO3 nanobeads (LMB‐NB) with uniform size and distribution were synthesized using a urea‐assisted microwave/solvothermal method. The potential application of LMB‐NBs as an anode for a lithium‐ion hybrid capacitor (Li‐AHC) was tested with a polyaniline‐nanofiber (PANI‐NF) cathode in a nonaqueous LiPF6 (1 M)–ethylene carbonate/dimethyl carbonate electrolyte. Cyclic voltammetry (CV) and charge–discharge (C/DC) studies revealed that the PANI‐NF/LMB‐NB cell showed an exceptional capacitance behavior between 0–3 V along with a prolonged cycle life. A discharge capacitance of about 125 F g−1, and energy and power densities of about 42 Wh kg−1 and 1500 W kg−1, respectively, could be obtained at a current density of 1 A g−1; those Li‐AHC values are higher relative to cells containing various lithium intercalation materials in nonaqueous electrolytes. In addition, the PANI‐NF/LMB‐NB cell also had an outstanding rate performance with a capacitance of 54 F g−1 and a power density of 3250 W kg−1 at a current density of 2.25 A g−1 and maintained 94 % of its initial value after 30 000 cycles. This improved capacitive performance with an excellent electrochemical stability could be the result of the morphological features and inherent conductive nature of the electroactive species.
A High‐Capacity, Low‐Cost Layered Sodium Manganese Oxide Material as Cathode for Sodium‐Ion Batteries
Authors: Guo Shaohua , Yu Haijun , Jian Zelang , Liu Pan , Zhu Yanbei , Guo Xianwei , Chen Mingwei , Ishida Masayoshi , Zhou Haoshen
Published: June 2014

A layered sodium manganese oxide material (NaMn3O5) is introduced as a novel cathode materials for sodium‐ion batteries. Structural characterizations reveal a typical Birnessite structure with lamellar stacking of the synthetic nanosheets. Electrochemical tests reveal a particularly large discharge capacity of 219 mAh g−1 in the voltage rang of 1.5–4.7 V vs. Na/Na+. With an average potential of 2.75 V versus sodium metal, layered NaMn3O5 exhibits a high energy density of 602 Wh kg−1, and also presents good rate capability. Furthermore, the diffusion coefficient of sodium ions in the layered NaMn3O5 electrode is investigated by using the galvanostatic intermittent titration technique. The results greatly contribute to the development of room‐temperature sodium‐ion batteries based on earth‐abundant elements.
A Polypyrrole Based Sensor for the Electrochemical Detection of OH Radicals
Authors: Gualandi Isacco , Guadagnini Lorella , Zappoli Sergio , Tonelli Domenica
Published: June 2014

Polypyrrole was used as sensitive material in the development of a new device employed for the indirect detection of OH radicals. The polypyrrole film was electrosynthesized on glassy carbon. The modified electrode was exposed to the OH radicals generated by Fenton reaction. As a result of the overoxidation the conductivity of the polymer diminished very much. The overoxidation (%) was directly proportional to the .OH amount that reached the electrode surface. ABTS.+, superoxide and alkylperoxy radicals did not interfere in the determination. The applicability of the device was demonstrated by estimating the .OH scavenging ability of ascorbic acid.
Supramolecular Amperometric Immunosensor for Detection of Human Chorionic Gonadotropin
Authors: Ortiz Mayreli , Wilson Lindsay , Botero Mary L. , Baker Priscilla , Iwuoha Emmanuel , Fragoso Alex , O'Sullivan Ciara K.
Published: June 2014

Human chorionic gonadotropin (hCG) is a hormone produced in high concentrations through the placental trophoblasts and is used for the detection of pregnancy and certain diseases. Here we explored a supramolecular strategy for the potentially substrateless amperometric detection of hCG. A carboxymethylcellulose (CMC) carrier was synthesised and trifunctionalised with anti‐βhCG antibody, horse radish peroxidase (HRP) and ferrocene (Fc) moieties. The ferrocene was used to house the functionalised CMC within the cavities of electrode surface immobilised cyclodextrin, via host‐guest interactions. hCG was detected via a sandwich format, forming an immunocomplex between the surface immobilised antibody and a glucose oxidase/lactate oxidase labelled secondary antibody. Following formation of the immunocomplex, lactate/glucose, which would typically be present in serum/urine samples, was added and the hydrogen peroxide formed detected at the electrode surface via the HRP‐Fc enzyme‐mediator couple. The work reported demonstrates a potential supramolecular platform for the detection of targets in blood/urine samples using endogenous substrates.
Adsorptive Cathodic Stripping Voltammetric Determination of Uranium(VI) in Presence of N‐Phenylanthranilic Acid
Authors: Rashidi Nassab H. , Bakhshi M. , Amini M. K.
Published: June 2014

N‐Phenylanthranilic acid was used as a complexing agent for determination of uranium(VI) by adsorptive cathodic stripping voltammetry. Under the optimal experimental conditions of the experimental parameters, the peak current was proportional to the concentration of U(VI) in the range 0.75–30 ng mL−1 and the detection limit was 0.036 ng mL−1. The influence of possible interferences was investigated. The method was applied for determination of uranium in waste water from uranium conversion facility and natural water samples. Application of the method for simultaneous determination of U(VI) and Cu(II) showed that these ions could be simultaneously determined in a single scan at relatively wide concentration range.
DPV and SWV Determination of Estrone Using a Cathodically Pretreated Boron‐Doped Diamond Electrode
Authors: Brocenschi Ricardo F. , Rocha‐Filho Romeu C. , Biaggio Sonia R. , Bocchi Nerilso
Published: June 2014

Voltammetric methods for estrone determination were developed using a cathodically pretreated BDD electrode with DPV or SWV. Analytical curves were obtained for estrone concentrations from 0.20 or 0.10 to 2.0 µmol L−1, for DPV or SWV, with detection limits of 0.20 and 0.10 µmol L−1, respectively. The SWV method was successfully applied in estrone recovery studies in different water matrices. Additionally, these recovery results were reasonably similar to those attained using HPLC/UV‐vis. Comparatively to other electroanalytical methods based on different carbon electrodes, the here‐reported novel methods yield very good results, being adequate for estrone determination in environmental samples.
Voltammetric Analysis of Naproxen in Graphite Electrodes and Its Determination in Pharmaceutical Samples
Authors: Aguilar‐Lira G. Y. , Romero G. A. Álvarez , Rojas‐Hernández A. , Páez‐Hernández M. E. , Rodríguez‐Ávila J. A. , Romero‐Romo M. A.
Published: June 2014

The present work discuses new findings in the electrochemistry of naproxen over graphite electrodes. This new approach, allows the proposal of a simple and competitive low‐cost method to carry out naproxen’s voltammetric quantification. Naproxen’s indirect quantification through an adsorption anodic wave was performed at a graphite bar electrode using differential pulse voltammetry. An anodic current maximum was recorded at a potential of −0.3 V referred to a saturated Ag/AgCl reference electrode. The calibration plot having a correlation coefficient of 0.990, sensibility of 4.19±0.62 µA cm3 µg−1, with detection and quantification limits of 0.68 and 3.3 µg cm−3, respectively.
Determination of Norepinephrine Alone and in the Presence of Ascorbic and Uric Acids Using a Gold Electrode Modified with Gold Nanoparticles and Self‐Assembled Layers of meso‐2,3‐Dimercaptosuccinic Acid
Authors: Łuczak Teresa
Published: June 2014

This paper reports on the modification of gold electrodes with self‐assembled layers (SAMs) composed of meso‐2,3‐dimercaptosuccinic acid, cysteamine and gold nanoparticles, respectively and their application to quantitative determination of norepinephrine alone and in the presence of ascorbic and uric acids in solution at pH 7. The modification was carried out on two kinds of templates: a bare gold electrode (2D electrode) and a gold electrode coated in the first step with gold nanoparticles (3D electrode). Cyclic voltammograms reveal an enhancement of the norepinephrine electrooxidation in comparison to a bare, (non‐modified) gold electrode. The oxidation peaks for norepinephrine, ascorbic acid and uric acid have a peak‐to‐peak separation that enables their selective determination even in a complex mixture.
Electrophoretic fingerprinting of benzodiazepine tablets in spike drinks
Authors: Sáiz Jorge , Ortega‐Ojeda Fernando , López‐Melero Lucía , Montalvo Gema , García‐Ruiz Carmen
Published: June 2014

Over the last few years, there has been an increase in the reports of drug‐facilitated crimes. The list of drugs associated with these crimes is extensive and benzodiazepines constitute one of the groups of substances more commonly used. The sedative properties, which characterize benzodiazepines, are enhanced when such drugs are combined with alcohol, being more attractive for committing these types of crimes. In this work, a capillary electrophoresis method was applied to the analysis of 63 different samples of club drinks spiked with benzodiazepine tablets. The resulting electropherograms were processed and analyzed with the chemometric multivariate techniques: principal component analysis (PCA) and soft independent modeling of class analogies (SIMCA) classification. The PCA results allowed a clear differentiation of each drug class in a 3D plot. In addition, the SIMCA classification model (5% significance level) showed that eight out of nine test samples were automatically assigned by software to their proper sample class. The conflicting sample was correctly classified in the Coomans’ plot (95% confidence). This novel approach based on the comparison of electrophoretic profiles of spiked drinks by chemometric tools allows determining the benzodiazepine used for drink spiking without the use of drug standards. Moreover, it provides an opportunity for the forensic laboratories to incorporate the identification capability provided by the electrophoretic fingerprinting of benzodiazepine solutions in existing or new databases.
Induced hydraulic pumping via integrated submicrometer cylindrical glass capillaries
Authors: Cao Zhen , Yobas Levent
Published: June 2014

Here, we report on a micropump that generates hydraulic pressure owing to a mismatch in EOF rates of microchannels and submicrometer cylindrical glass capillaries integrated on silicon. The electrical conductance of such capillaries in the dilute limit departs from bulk linear behavior as well as from the surface‐charge‐governed saturation in nanoslits that is well described by the assumption of a constant surface charge density. The capillaries show rather a gradual decrease in conduction at low salt concentrations, which can be explained more aptly by a variable surface charge density that accounts for chemical equilibrium of the surface. The micropump uses a traditional cross‐junction structure with ten identical capillaries integrated in parallel on a side arm and each with a 750 nm diameter and 3 mm length. For an applied voltage of 700 V, a hydraulic pressure up to 5 kPa is generated with a corresponding flow velocity nearly 3 mm/s in a straight field‐free branch 20 μm wide, 10 μm deep, and 10 mm long. The micropump utility has been demonstrated in an open tubular LC of three fluorescently labeled amino acids in just less than 20 s with minimal plate height values between 3 and 7 μm. The submicrometer capillaries are self‐enclosed and produced through a unique process that does not require high‐resolution advanced lithography or wafer‐bonding techniques to define their highly controlled precise structures.
Core‐shell structure microcapsules with dual pH‐responsive drug release function
Authors: Yang Chih‐Hui , Wang Chih‐Yu , Grumezescu Alexandru Mihai , Wang Andrew H.‐J. , Hsiao Ching‐Ju , Chen Zu‐Yu , Huang Keng‐Shiang
Published: June 2014

We report dual pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)‐shell (chitosan) structure with dual pH‐responsive drug release function. The fabricated core‐shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core‐shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core‐shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core‐shell microcapsules were a potential candidate of dual‐drug carriers.
First genetic analysis of Cryptosporidium from humans from Tasmania, and identification of a new genotype from a traveller to Bali
Authors: Koehler Anson V. , Whipp Margaret , Hogg Geoff , Haydon Shane R. , Stevens Melita A. , Jex Aaron R. , Gasser Robin B.
Published: June 2014

Little is known about the molecular composition of Cryptosporidium species from humans living in the insular state of Tasmania, Australia. In the present study, we genetically characterized 82 samples of Cryptosporidium from humans following conventional coproscopic testing in a routine, diagnostic laboratory. Using a PCR‐coupled single‐strand conformation polymorphism (SSCP) technique, targeting portions of the small subunit rRNA (SSU), and 60 kDa glycoprotein (gp60) loci, we identified two species of Cryptosporidium, including C. hominis (subgenotypes IbA10G2, IdA16, IeA12G3T3, and IfA19G1) and C. parvum (IIaA16G1R1 and IIaA18G3), and a new operational taxonomic unit (OTU) that genetically closely resembled C. wrairi. This OTU was further characterized using markers in the actin, Cryptosporidium oocyst wall protein (COWP), and 70 kDa heat shock protein (hsp70) genes. This study provides the first characterization of species and genotypes of Cryptosporidium from Tasmania, and presents clear genetic evidence, using five independent genetic loci, for a new genotype or species of Cryptosporidium in a Tasmanian person with a recent history of travelling to Bali, Indonesia. It would be interesting to undertake detailed molecular‐based studies of Cryptosporidium in Indonesia and neighbouring countries, in conjunction with morphological and experimental investigations of new genotypes.
Rational selection of alternative, environmentally compatible surfactants for biotechnological production of pharmaceuticals—A step toward green biotechnology
Authors: Straub Jürg Oliver , Shearer Russel , Studer Martin
Published: June 2014

The biotechnological production of pharmaceutical active substances needs ancillary substances. Surfactants are used at the end of the cell culture as a protection against potential viral or bacterial contamination and to lyse the producing cells for isolation and purification of the products. To find a replacement for a surfactant that had raised environmental concern, environmentally relevant data for potential alternatives were searched for in the literature. Significant data gaps were filled with additional tests: biodegradability, algal growth inhibition, acute daphnid immobilization and chronic daphnid reproduction toxicity, acute fish toxicity, and activated sludge respiration inhibition. The results were used to model removal in the wastewater treatment plants (WWTPs) serving 3 biotechnological production sites in the Roche Group. Predicted environmental concentrations (PECs) were calculated using realistic amounts of surfactants and site-specific wastewater fluxes, modeled removals for the WWTPs and dilution factors by the respective receiving waters. Predicted no-effect concentrations (PNECs) were derived for WWTPs and for both fresh and marine receiving waters as the treated wastewater of 1 production site is discharged into a coastal water. This resulted in a spreadsheet showing PECs, PNECs, and PEC ÷ PNEC risk characterization ratios for the WWTPs and receiving waters for all investigated surfactants and all 3 sites. This spreadsheet now serves as a selection support for the biotechnological developers. This risk-based prioritization of surfactants is a step toward green biotechnological production. Environ Toxicol Chem 2014; 33:2140–2146. © 2014 SETAC
Leaf micromorphology and leaf glandular hair ontogeny of Myoporum bontioides A. Gray
Authors: Das Sauren , Sheue Chiou‐Rong , Yang Yuen‐Po
Published: June 2014

Myoporum bontioides A. Gray (Myoporaceae), a red list plant in Japan, is restricted to only a few East Asian countries like China, Japan and Taiwan, associated to some true mangroves. The leaf is isolateral and has a thick cuticle; stomata are anomocytic, sunken and have a beak‐shaped cuticular outgrowth at the inner and outer side of the stomatal pore (ledges); profuse glandular hairs are scattered on both leaf surfaces of young leaves. The mesophyll is compact with palisade and spongy parenchyma cells in the young stage, but at maturity profuse intercellular spaces can be observed. Secretory ducts occur in young leaves. Pear‐shaped glandular hairs protrude from the epidermal layer. Hair primordia are well distinct by their larger size and undergo divisions to produce two laterally placed basal cells, two stalk cells and four radiating terminal cells. The cuticle layers of the terminal cells are often separated from the cell wall to form a space, in which ions accumulate for excretion. Inner walls of the basal cells are connected with the mesophyll. Though ontogeny and structure of glandular hairs have resemblance to typical mangroves, considering leaf micromorphology, this plant is better termed as “mangrove associate” instead of “true mangrove”. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Community programmes for coronary heart disease in Spanish primary care
Authors: Frigola‐Capell Eva , van Lieshout Jan , Muñoz Miguel A. , Verdú‐Rotellar Jose , Orfila Francesc , Suñol Rosa , Wensing Michel
Published: June 2014

Objective

To explore the added value of community‐orientated programmes aimed at enhancing healthy lifestyles associated with the key components of cardiovascular risk management (CVRM) in coronary heart disease (CHD) patients.

Methods

Observational study in Spain, including 36 practices, 36 health professionals, and 722 CHD patients (mean (SD) age 72 (11.73)). Our predictor variable of interest was reported deliveries from primary care practices (PCPs) concerning community‐orientated programmes such as physical exercise and smoking cessation groups. Data were obtained through structured questionnaires administered to PCP health professionals. Our CVRM outcome measures were as follows: recorded risk factors, drug prescriptions, and intermediate patient outcomes (blood pressure levels, low‐density lipoprotein cholesterol, and body mass index).

Results

Thirty practices delivered community programmes: most delivered one [17 (47.2%) practices] or two [11 (30.5%) practices]. These educational programmes aimed to encourage enhanced healthy lifestyles through group counselling sessions, mailed print material, and one‐to‐one counselling. In PCPs delivering community programmes, more patients received antihypertensives (89.7%), antiplatelet therapy (80.5%), and statins (70.8%) than those PCPs without programmes, although there were no statistically significant differences between them.

Conclusions

No evidence was found for the added value of community‐orientated CVRM programmes that could help health professionals refine criteria when including CHD patients in preventive programmes. Copyright © 2014 John Wiley & Sons, Ltd.
A prognostic classifier consisting of 17 circulating cytokines is a novel predictor of overall survival for metastatic colorectal cancer patients
Authors: Chen Zhi‐Yuan , He Wen‐Zhuo , Peng Li‐Xia , Jia Wei‐Hua , Guo Rong‐Ping , Xia Liang‐Ping , Qian Chao‐Nan
Published: June 2014

We aimed to determine the prognostic values of 39 circulating cytokines in Chinese patients with metastatic colorectal cancer (CRC) and to develop a novel cytokine‐based prognostic classifier (CBPC) for prognostic prediction. A total of 176 patients were divided into two cohorts based on the date of first‐line chemotherapy. The first 99 cases were assigned to the training cohort, and the remaining 77 cases were assigned to the validation cohort. Thirty‐nine cytokines were simultaneously analyzed in the patient serum samples using multiplex bead‐based Luminex technology. We used support vector machine‐based methods and Cox proportional hazards models to develop a CBPC from the training cohort, which we then validated using the second patient cohort. Univariate analysis showed that FGF‐2, TGFα, Flt‐3L, GM‐CSF, INFα2, GRO, IL‐10, MCP‐3, MDC, sIL‐2Rα, IL‐2, IL‐7, IL‐8, MCP‐1, MIP‐1β, TNFα and VEGF were significant risk factors affecting the overall survival (OS) of both the training cohort and the validation cohort. We developed a CBPC to predict the OS of metastatic CRC patients using these 17 cytokines (sensitivity, 0.835; specificity, 0.800). In the validation cohort, the CBPC was found to have significant power in predicting the OS of metastatic CRC patients. Our study showed that there were significant associations between cytokine expression and prognosis of the patients with metastatic CRC. The CBPC that we developed includes multiple circulating cytokines and may serve as a novel screening tool for identifying metastatic CRC patients with a high risk of short OS. These high‐risk individuals may also be suitable for cytokine‐targeted therapies.
Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China
Authors: Kim Christopher , Gao Yu‐Tang , Xiang Yong‐Bing , Barone‐Adesi Francesco , Zhang Yawei , Hosgood H. Dean , Ma Shuangge , Shu Xiao‐ou , Ji Bu‐Tian , Chow Wong‐Ho , Seow Wei Jie , Bassig Bryan , Cai Qiuyin , Zheng Wei , Rothman Nathaniel , Lan Qing
Published: June 2014

Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case–control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use, and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and 20 or more years of using coal with poor ventilation (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation.
MicroRNA expression signatures for the prediction of BRCA1/2 mutation‐associated hereditary breast cancer in paraffin‐embedded formalin‐fixed breast tumors
Authors: Tanic Miljana , Yanowski Kira , Gómez‐López Gonzalo , Socorro Rodriguez‐Pinilla María , Marquez‐Rodas Iván , Osorio Ana , Pisano David G. , Martinez‐Delgado Beatriz , Benítez Javier
Published: June 2014

Screening for germline mutations in breast cancer‐associated genes BRCA1 and BRCA2 is indicated for patients with breast cancer from high‐risk breast cancer families and influences both treatment options and clinical management. However, only 25% of selected patients test positive for BRCA1/2 mutation, indicating that additional diagnostic biomarkers are necessary. We analyzed 124 formalin‐fixed paraffin‐embedded (FFPE) tumor samples from patients with hereditary (104) and sporadic (20) invasive breast cancer, divided into two series (A and B). Microarray expression profiling of 829 human miRNAs was performed on 76 samples (Series A), and bioinformatics tool Prophet was used to develop and test a microarray classifier. Samples were stratified into a training set (n = 38) for microarray classifier generation and a test set (n = 38) for signature validation. A 35‐miRNA microarray classifier was generated for the prediction of BRCA1/2 mutation status with a reported 95% (95% CI = 0.88–1.0) and 92% (95% CI: 0.84–1.0) accuracy in the training and the test set, respectively. Differential expression of 12 miRNAs between BRCA1/2 mutation carriers versus noncarriers was validated by qPCR in an independent tumor series B (n = 48). Logistic regression model based on the expression of six miRNAs (miR‐142‐3p, miR‐505*, miR‐1248, miR‐181a‐2*, miR‐25* and miR‐340*) discriminated between tumors from BRCA1/2 mutation carriers and noncarriers with 92% (95% CI: 0.84–0.99) accuracy. In conclusion, we identified miRNA expression signatures predictive of BRCA1/2 mutation status in routinely available FFPE breast tumor samples, which may be useful to complement current patient selection criteria for gene testing by identifying individuals with high likelihood of being BRCA1/2 mutation carriers.
Reproducibility of Results in Preclinical Studies: A Perspective From the Bone Field
Authors: Manolagas Stavros C , Kronenberg Henry M
Published: June 2014

The biomedical research enterprise—and the public support for it—is predicated on the belief that discoveries and the conclusions drawn from them can be trusted to build a body of knowledge which will be used to improve human health. As in all other areas of scientific inquiry, knowledge and understanding grow by layering new discoveries upon earlier ones. The process self-corrects and distills knowledge by discarding false ideas and unsubstantiated claims. Although self-correction is inexorable in the long-term, in recent years biomedical scientists and the public alike have become alarmed and deeply troubled by the fact that many published results cannot be reproduced. The chorus of concern reached a high pitch with a recent commentary from the NIH Director, Francis S. Collins, and Principal Deputy Director, Lawrence A. Tabak, and their announcement of specific plans to enhance reproducibility of preclinical research that relies on animal models. In this invited perspective, we highlight the magnitude of the problem across biomedical fields and address the relevance of these concerns to the field of bone and mineral metabolism. We also suggest how our specialty journals, our scientific organizations, and our community of bone and mineral researchers can help to overcome this troubling trend. © 2014 American Society for Bone and Mineral Research.
Human Osteoclasts Are Inducible Immunosuppressive Cells in Response to T cell–Derived IFN-γ and CD40 Ligand In Vitro
Authors: Li Haiyan , Lu Yong , Qian Jianfei , Zheng Yuhuan , Zhang Mingjun , Bi Enguang , He Jin , Liu Zhiqiang , Xu Jingda , Gao Jerry Y , Yi Qing
Published: June 2014

Osteoclasts (OCs) are bone resorbing cells whose activity can be regulated by activated T cells and their cytokines. However, the immune function of OCs is largely unknown. In this study, we found that as bystanders, human OCs effectively suppressed T-cell proliferation induced by allogeneic, microbial antigenic, and T-cell receptor stimuli in vitro. Mechanism studies revealed that T cell–derived IFN-γ and CD40 ligand (CD40L) induced the expression of indoleamine 2,3-dioxygenase (IDO) in OCs, which mediated the immunosuppressive function on T-cell proliferation through depleting tryptophan. Neutralizing IFN-γ and blocking CD40L, or silencing or inhibiting IDO in OCs restored T-cell proliferation in the presence of OCs. Our data reveal a novel function of human OCs as inducible immunosuppressive cells, and a feedback loop between OCs and activated T cells. Thus, this study provides new insight into the mechanism of the immunosuppressive function of OCs, and may be helpful for developing novel therapeutic strategies for human diseases involving both the bone and immune systems. © 2014 American Society for Bone and Mineral Research.
SH3BP2 Cherubism Mutation Potentiates TNF-α–Induced Osteoclastogenesis via NFATc1 and TNF-α–Mediated Inflammatory Bone Loss
Authors: Mukai Tomoyuki , Ishida Shu , Ishikawa Remi , Yoshitaka Teruhito , Kittaka Mizuho , Gallant Richard , Lin Yi-Ling , Rottapel Robert , Brotto Marco , Reichenberger Ernst J , Ueki Yasuyoshi
Published: June 2014

Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI) mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)-α production and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2KI/KI). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α–mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α–mediated osteoclast formation and bone loss. Here, we show that bone marrow–derived M-CSF–dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2KI/+) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and phospholipase Cγ2 (PLCγ2) phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α–induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for the treatment of bone loss in cherubism as well as in other inflammatory bone disorders. © 2014 American Society for Bone and Mineral Research.
Detecting False Intent Amongst Small Cells of Suspects: Single Versus Repeated Interviews
Authors: Mac Giolla Erik , Granhag Pär Anders
Published: June 2014

The study adds to the growing research field of true and false intentions. Specifically, we examined the benefit of asking unanticipated questions when interviewing groups of suspects on repeated occasions. Participants were divided into truth tellers and liars and were further divided into groups of three. Truth tellers planned a neutral task. Liars planned a mock crime and additionally prepared a cover‐story—thematically similar to the truth tellers' task—to be used if they were apprehended. Participants were intercepted after planning their tasks. In subsequent interviews, participants were asked anticipated questions on their intentions and unanticipated questions on the planning of their intentions. Participants were interviewed once in Experiment 1 (N = 132) and three times in Experiment 2 (N = 123). Truth tellers provided longer and more detailed answers than liars and had higher levels of within‐group consistency compared with liars. This was the case for answers to both anticipated and unanticipated questions. No differences between truth tellers and liars were found for between‐statement consistency. Repeated interviews had minimal effect on statement length or within‐group consistency. The results highlight within‐group consistency as an important cue to deceit. However, a number of limitations to the unanticipated questions approach were evident. Copyright © 2014 John Wiley & Sons, Ltd.
Adrenocorticotropin hormone 1‐39 promotes proliferation and differentiation of oligodendroglial progenitor cells and protects from excitotoxic and inflammation‐related damage
Authors: Benjamins Joyce A. , Nedelkoska Liljana , Lisak Robert P.
Published: June 2014

Oligodendroglia (OL) are highly susceptible to damage and, like neurons, are terminally differentiated. It is important to protect OL precursors (OPC) because they are reservoirs of differentiating cells capable of myelination following perinatal insult and remyelination in white matter diseases, including multiple sclerosis (MS). Patients with relapsing‐remitting MS are commonly treated with high‐dose corticosteroids (CS) when experiencing an exacerbation. Adrenocorticotropin hormone (ACTH), a primary component of another approved MS exacerbation treatment, is a melanocortin peptide that stimulates production of CS by the adrenals. Melanocortin receptors are also found in the central nervous system (CNS) and on immune cells. ACTH is produced within the CNS and may have CS‐independent effects on glia. We found that ACTH 1‐39 stimulated proliferation of OPC, and to a lesser extent astroglia (AS) and microglia (MG), in rat glial cultures. ACTH accelerated differentiation of PDGFRα+ OPC to a later stage marked by galactolipid expression and caused greater expansion of OL myelin‐like sheets compared with untreated cells. Protective effects of ACTH on OPC were assessed by treating cultures with selected toxic agents, with or without ACTH. At 200 nM, ACTH protected OPC from death induced by staurosporine, glutamate, NMDA, AMPA, kainate, quinolinic acid, H2O2, and slow NO release, but not against kynurenic acid or rapid NO release. These agents and ACTH were not toxic to AS or MG. Our findings indicate that ACTH 1‐39 provides benefits by increasing the number of OPC, accelerating their development into mature OL, and reducing OPC death from toxic insults. © 2014 Wiley Periodicals, Inc.
The N‐terminal fragment of the β‐amyloid precursor protein of Alzheimer's disease (N‐APP) binds to phosphoinositide‐rich domains on the surface of hippocampal neurons
Authors: Dawkins Edgar , Gasperini Robert , Hu Yanling , Cui Hao , Vincent Adele J. , Bolós Marta , Young Kaylene M. , Foa Lisa , Small David H.
Published: June 2014

The function of the β‐amyloid precursor protein (APP) of Alzheimer's disease is poorly understood. The secreted ectodomain fragment of APP (sAPPα) can be readily cleaved to produce a small N‐terminal fragment (N‐APP) that contains heparin‐binding and metal‐binding domains and that has been found to have biological activity. In the present study, we examined whether N‐APP can bind to lipids. We found that N‐APP binds selectively to phosphoinositides (PIPs) but poorly to most other lipids. Phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2)‐rich microdomains were identified on the extracellular surface of neurons and glia in primary hippocampal cultures. N‐APP bound to neurons and colocalized with PIPs on the cell surface. Furthermore, the binding of N‐APP to neurons increased the level of cell‐surface PI(4,5)P2 and phosphatidylinositol 3,4,5‐trisphosphate. However, PIPs were not the principal cell‐surface binding site for N‐APP, because N‐APP binding to neurons was not inhibited by a short‐acyl‐chain PIP analogue, and N‐APP did not bind to glial cells which also possessed PI(4,5)P2 on the cell surface. The data are explained by a model in which N‐APP binds to two distinct components on neurons, one of which is an unidentified receptor and the second of which is a PIP lipid, which binds more weakly to a distinct site within N‐APP. Our data provide further support for the idea that N‐APP may be an important mediator of APP's biological activity. © 2014 Wiley Periodicals, Inc.