bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in
DCC
Cause Congenital Mirror Movements
Authors: Srour Myriam , Rivière Jean-Baptiste , Pham Jessica M. T. , Dubé Marie-Pierre , Girard Simon , Morin Steves , Dion Patrick A. , Asselin Géraldine , Rochefort Daniel , Hince Pascale , Diab Sabrina , Sharafaddinzadeh Naser , Chouinard Sylvain , Théoret Hugo , Charron Frédéric , Rouleau Guy A.
Published: April 2010

Humans who display involuntary symmetrical limb movements carry mutations in a gene required for nerve growth across the midline.
The Impacts of Innovation
Technological Medicine
The Changing World of Doctors and Patients

by Stanley Joel Reiser

Cambridge University Press, Cambridge, 2009. 245 pp. $30, £20. ISBN 9780521835695.
Authors: Mathis Richard S.
Published: April 2010

Through a series of case studies, Reiser offers a historical perspective on the invention, use, and consequences of medical technologies.
Frog DNA Yields Clues to Vertebrate Genome Evolution
Authors: Pennisi Elizabeth
Published: April 2010

On page
633
of this week's issue of
Science
, researchers describe the sequence of the Western clawed frog,
Xenopus tropicalis
, the first member of the amphibian branch of the tree of life whose genome has been sequenced.
Deal to Legalize Whaling Would Sideline Science
Authors: Morell Virginia
Published: April 2010

In a bid to tighten the organization's grip on its members' whaling and reduce the number of whales killed, the International Whaling Commission has proposed that in exchange for temporarily narrowing loopholes, Japan, Norway, and Iceland would be allowed to commercially hunt whales for 10 years.
Paul Nurse Chosen to Head Royal Society
Authors: Kaiser Jocelyn
Published: April 2010

Nobel Prize–winning biologist Paul Nurse is stepping down as president of Rockefeller University in New York City to become president of the Royal Society in London, the United Kingdom's science academy.
Spunky Hayabusa Heads Home With Possible Payload
Authors: Normile Dennis
Published: April 2010

A record-setting Japanese mission to an asteroid is due to land in June after overcoming a 7-year history of mishaps.
Development of a Recombinant Epsilon Toxoid Vaccine against Enterotoxemia and Its Use as a Combination Vaccine with Live Attenuated Sheep Pox Virus against Enterotoxemia and Sheep Pox
Authors: Chandran Dev , Naidu Sureddi Satyam , Sugumar Parthasarathy , Rani Gudavalli Sudha , Vijayan Shahana Pallichera , Mathur Deepika , Garg Lalit C. , Srinivasan Villuppanoor Alwar
Published: April 2010

Sheep pox and enterotoxemia are important diseases of sheep, and these diseases cause severe economic losses to sheep farmers. The present study was undertaken to evaluate the potential of formaldehyde-inactivated recombinant epsilon toxin as a vaccine candidate. The potency of the recombinant epsilon toxoid with aluminum hydroxide as an adjuvant in sheep was determined. Vaccinated sheep were protected against enterotoxemia, with potency values of >5 IU being protective. Further, the use of this construct in a combination vaccine against sheep pox resulted in the sheep being protected against both sheep pox and enterotoxemia.
Options for Inactivation, Adjuvant, and Route of Topical Administration of a Killed, Unencapsulated Pneumococcal Whole-Cell Vaccine
Authors: Lu Ying-Jie , Yadav Puja , Clements John D. , Forte Sophie , Srivastava Amit , Thompson Claudette M. , Seid Robert , Look Jee , Alderson Mark , Tate Andrea , Maisonneuve Jean-François , Robertson George , Anderson Porter W. , Malley Richard
Published: April 2010

We previously reported that ethanol-killed cells of a noncapsulated strain of
Streptococcus pneumoniae
, given intranasally with cholera toxin as an adjuvant, protect rats against pneumonia and mice against colonization of the nasopharynx and middle ear by capsulated pneumococci of various serotypes. The acceleration of pneumococcal clearance from the nasopharynx in mice is CD4
+
T cell-dependent and interleukin 17A (IL-17A) mediated and can be antibody independent. Here, anticipating human studies, we have demonstrated protection with a new vaccine strain expressing a nonhemolytic derivative of pneumolysin and grown in bovine-free culture medium. Killing the cells with chloroform, trichloroethylene, or beta-propiolactone—all used without postinactivation washing—produced more-potent immunogens than ethanol, and retention of soluble components released from the cells contributed to protection. Two sequential intranasal administrations of as little as 1 μg of protein (total of cellular and soluble combined) protected mice against nasopharyngeal challenge with pneumococci. Nontoxic single and double mutants of
Escherichia coli
heat-labile toxin were effective as mucosal adjuvants. Protection was induced by the sublingual and buccal routes, albeit requiring larger doses than when given intranasally. Protection was likewise induced transdermally with sonicates of the killed-cell preparation. Thus, this whole-cell antigen can be made and administered in a variety of ways to suit the manufacturer and the vaccination program and is potentially a solution to the need for a low-cost vaccine to reduce the burden of childhood pneumococcal disease in low-income countries.
Evaluation of the Bio-Rad BioPlex 2200 Syphilis Multiplex Flow Immunoassay for the Detection of IgM- and IgG-Class Antitreponemal Antibodies
Authors: Gomez E. , Jespersen D. J. , Harring J. A. , Binnicker M. J.
Published: April 2010

The laboratory diagnosis of syphilis is based primarily upon serologic findings. Historically, serologic testing for syphilis has relied on assays such as rapid plasma reagin, fluorescent treponemal antibody absorption,
Treponema pallidum
particle agglutination (TP-PA), and more recently, enzyme immunoassay (EIA). In this study, we evaluated the performance of a novel multiplex flow immunoassay (BioPlex 2200 Syphilis; Bio-Rad Laboratories, Hercules, CA) for the detection of antitreponemal IgG- and IgM-class antibodies. Serum specimens (
n
= 1,008) submitted for routine treponema-specific antibody testing by syphilis IgM and IgG EIA (Trep-Chek; Phoenix-Biotech, Mississauga, Ontario, Canada) were also analyzed by the BioPlex Syphilis multiplex assay. Specimens showing discordant results were repeat tested, with further discrepancies being arbitrated by TP-PA. Compared directly to the results of EIA, the BioPlex IgG assay demonstrated 98.7% (77/78) sensitivity and 99.4% (916/930) specificity. Compared to the Trep-Chek IgM EIA, the BioPlex IgM assay showed 80% (4/5) sensitivity and 97.9% (652/666) specificity. These results indicate that the BioPlex Syphilis multiplex assay shows similar serological agreement with EIA while allowing for a fully automated random-access platform that provides faster (1.7 h for 100 samples versus 4.5 h by EIA) and higher-throughput (800 samples per 9 h versus 200 samples by EIA) analysis of the syphilis serologic response.
A Low-Molecular-Weight Entry Inhibitor of both CCR5- and CXCR4-Tropic Strains of Human Immunodeficiency Virus Type 1 Targets a Novel Site on gp41
Authors: Murray Edward J. , Leaman Daniel P. , Pawa Nishant , Perkins Hannah , Pickford Chris , Perros Manos , Zwick Michael B. , Butler Scott L.
Published: April 2010

A low-molecular-weight human immunodeficiency virus type 1 (HIV-1) inhibitor, PF-68742 (molecular weight, 573), has been identified in a high-throughput screen for compounds that block HIV-1 envelope glycoprotein (Env)-mediated fusion. The compound is shown to be potent against R5 and X4 isolates in both cell-cell fusion and antiviral assays (50% effective concentrations of ∼0.1 to 1 μM). Postfusion and HIV-1 pseudotyping control experiments confirm that PF-68742 is an entry inhibitor with Env as the specific target for antiviral action. PF-68742 was not able to block binding of monomeric gp120 to soluble CD4 or the binding of gp120:CD4 complexes to cell-associated CCR5, thus distinguishing PF-68742 from described gp120 antagonists and coreceptor binders. Escape variants of HIV-1
NL4-3
were selected, and all resistant viruses were found to contain a common G514R (HxB2 numbering) mutation in Env, located proximal to the furin cleavage site in the fusion peptide of gp41. When introduced into wild-type NL4-3 gp41, G514R conferred resistance to PF-68742. Resistance via G514R is shown to be associated with enhancement of virion infectivity by PF-68742 that may result from altered properties of inhibitor-bound Env, rather than from a loss of compound binding. Wild-type viruses and those with substitutions in the disulfide loop (DSL) region of gp41 were also examined for PF-68742 sensitivity. Here, complete resistance to PF-68742 was found to occur through changes outside of position 514, including in the gp41 DSL region. The results highlight PF-68742 as a starting point for novel therapies against HIV-1 and provide new insights into models of Env-mediated fusion.
Two Domains of the V Protein of Virulent Canine Distemper Virus Selectively Inhibit STAT1 and STAT2 Nuclear Import
Authors: Röthlisberger Anne , Wiener Dominique , Schweizer Matthias , Peterhans Ernst , Zurbriggen Andreas , Plattet Philippe
Published: April 2010

Canine distemper virus (CDV) causes in dogs a severe systemic infection, with a high frequency of demyelinating encephalitis. Among the six genes transcribed by CDV, the P gene encodes the polymerase cofactor protein (P) as well as two additional nonstructural proteins, C and V; of these V was shown to act as a virulence factor. We investigated the molecular mechanisms by which the P gene products of the neurovirulent CDV A75/17 strain disrupt type I interferon (IFN-α/β)-induced signaling that results in the establishment of the antiviral state. Using recombinant knockout A75/17 viruses, the V protein was identified as the main antagonist of IFN-α/β-mediated signaling. Importantly, immunofluorescence analysis illustrated that the inhibition of IFN-α/β-mediated signaling correlated with impaired STAT1/STAT2 nuclear import, whereas the phosphorylation state of these proteins was not affected. Coimmunoprecipitation assays identified the N-terminal region of V (VNT) responsible for STAT1 targeting, which correlated with its ability to inhibit the activity of the IFN-α/β-mediated antiviral state. Conversely, while the C-terminal domain of V (VCT) could not function autonomously, when fused to VNT it optimally interacted with STAT2 and subsequently efficiently suppressed the IFN-α/β-mediated signaling pathway. The latter result was further supported by a single mutation at position 110 within the VNT domain of CDV V protein, resulting in a mutant that lost STAT1 binding while retaining a partial STAT2 association. Taken together, our results identified the CDV VNT and VCT as two essential modules that complement each other to interfere with the antiviral state induced by IFN-α/β-mediated signaling. Hence, our experiments reveal a novel mechanism of IFN-α/β evasion among the morbilliviruses.
Semliki Forest Virus-Induced Endoplasmic Reticulum Stress Accelerates Apoptotic Death of Mammalian Cells
Authors: Barry Gerald , Fragkoudis Rennos , Ferguson Mhairi C. , Lulla Aleksei , Merits Andres , Kohl Alain , Fazakerley John K.
Published: April 2010

The alphavirus Semliki Forest virus (SFV) and its derived vectors induce apoptosis in mammalian cells. Here, we show that apoptosis is associated with the loss of mitochondrial membrane potential followed by the activation of caspase-3, caspase-8, and caspase-9. Cell death can be partially suppressed by treatment with the pan-caspase inhibitor zVAD-fmk. To determine the role of SFV structural proteins in cell death, the temporal course of cell death was compared in cells infected with SFV and cells infected with SFV virus replicon particles (VRPs) lacking some or all of the virus structural genes. In the absence of virus structural proteins, cell death was delayed. The endoplasmic reticulum (ER) stress response, as determined by the splicing of X-box binding protein 1 (XBP1) transcripts and the activation of caspase-12, was activated in virus-infected cells but not in VRP (SFV lacking structural genes)-infected cells. The C/EBP-homologous protein (CHOP) was upregulated by both virus and VRP infections. The virus envelope proteins but not the virus capsid protein triggered ER stress. These results demonstrate that in NIH 3T3 cells, SFV envelope glycoproteins trigger the unfolded protein response of the ER and accelerate apoptotic cell death initiated by virus replicase activity.
GENERALIZED COHERENT STATES FOR THE SPHERICAL HARMONICS $Y_{m}^{m}(\theta,\phi)$
Authors: FAKHRI H. , MOJAVERI B.
Published: April 2010

The associated Legendre functions [Formula: see text] for a given l-m, may be taken into account as the increasing infinite sequences with respect to both indices l and m. This allows us to construct the exponential generating functions for them in two different methods by using Rodrigues formula. As an application then we present a scheme to construct generalized coherent states corresponding to the spherical harmonics [Formula: see text].
INNOVATIONS IN THE CMS TRACKER ELECTRONICS
Authors: HALL G.
Published: April 2010

The CMS silicon microstrip tracker readout system is unprecedented in size, with over nine million channels. It is an analogue readout system, implemented using CMOS ASICs and linear, semiconductor laser transmitters which send pulse height data off-detector for digitisation and the first level of data processing. The basic components which define the architecture originated in R&D projects in the early 1990s and were crucial in allowing this system to be realised. The availability of several key technologies was critical to achieving the design preferences, and the components and technologies were utilised also to build the control and monitoring system and, later, to implement critical elements of other CMS sub-detector systems. The background to the technology choices and early development of the system is described and an attempt is made to draw some lessons which could be relevant for the future.
Upregulation of store-operated Ca2+ entry in dystrophic mdx mouse muscle
Authors: Edwards Joshua N. , Friedrich Oliver , Cully Tanya R. , von Wegner Frederic , Murphy Robyn M. , Launikonis Bradley S.
Published: April 2010

Store-operated Ca2+ entry (SOCE) is an important mechanism in virtually all cells. In adult skeletal muscle, this mechanism is highly specialized for the rapid delivery of Ca2+ from the transverse tubule into the junctional cleft during periods of depleting Ca2+ release. In dystrophic muscle fibers, SOCE may be a source of Ca2+ overload, leading to cell necrosis. However, this possibility is yet to be examined in an adult fiber during Ca2+ release. To examine this, Ca2+ in the tubular system and cytoplasm were simultaneously imaged during direct release of Ca2+ from sarcoplasmic reticulum (SR) in skeletal muscle fibers from healthy (wild-type, WT) and dystrophic mdx mouse. The mdx fibers were found to have normal activation and deactivation properties of SOCE. However, a depression of the cytoplasmic Ca2+ transient in mdx compared with WT fibers was observed, as was a shift in the SOCE activation and deactivation thresholds to higher SR Ca2+ concentrations ([Ca2+]SR). The shift in SOCE activation and deactivation thresholds was accompanied by an approximately threefold increase in STIM1 and Orai1 proteins in dystrophic muscle. While the mdx fibers can introduce more Ca2+ into the fiber for an equivalent depletion of [Ca2+]SR via SOCE, it remains unclear whether this is deleterious.
Estrogen receptor mediates the effects of pseudoprotodiocsin on adipogenesis in 3T3-L1 cells
Authors: Xiao Jing , Wang Nai-li , Sun Bing , Cai Guo-ping
Published: April 2010

Estrogen receptors (ERs) play a pivotal role in adipogenesis; therefore, compounds targeting ERs may also affect fat formation. Recent studies have shown that the Dioscorea plant (commonly called yam) exhibits an antiobesity effect on rodents. However, the active compounds and underlying mechanisms responsible for this effect are not yet fully understood. We evaluated the effects of pseudoprotodiocsin (PPD), a steroid saponin from Dioscorea nipponica Makino (a type of Dioscorea), on adipogenesis and the mechanisms underlying this effect. Treatment with PPD at the onset of adipogenic differentiation resulted in significantly decreased adipogenesis in both in vitro and in vivo experimental systems. An increased amount of ERα mRNA, protein, and the accumulation of ERα in the nucleus were also observed. However, the expression pattern of ERβ was not altered. Furthermore, the antiadipogenic effect of PPD was found to be ER dependent. It was also accompanied by the decreased expression of several genes involved in adipogenesis, including lipoprotein lipase (LPL), leptin, CCAAT/enhancer-binding-protein-α (C/EBPα), and peroxisome proliferator-activated receptor-γ (PPARγ), as well as the increased expression of some negative factors of adipogenesis, including preadipocyte factor 1 (Pre-1), GATA-binding protein 2 (GATA-2), GC-induced leucine-zipper protein (GILZ), and C/EBP homologous protein (CHOP-10). In addition to its estrogenic action, PPD also abolished the p38 mitogen-activated protein kinase (p38 MAPK) activation. Our results suggest that PPD inhibits adipogenesis in an ER-dependent manner and induces the expression of ERα. These findings may provide a lead toward a novel agent that can be used to treat obesity.
Central nociceptin/orphanin FQ system elevates food consumption by both increasing energy intake and reducing aversive responsiveness
Authors: Olszewski Pawel K. , Grace Martha K. , Fard Shahrzad Shirazi , Le Grevès Madeleine , Klockars Anica , Massi Maurizio , Schiöth Helgi B. , Levine Allen S.
Published: April 2010

Nociceptin/orphanin FQ (N/OFQ), the nociceptin opioid peptide (NOP) receptor ligand, increases feeding when injected centrally. Initial data suggest that N/OFQ blocks the development of a conditioned taste aversion (CTA). The current project further characterized the involvement of N/OFQ in the regulation of hunger vs. aversive responses in rats by employing behavioral, immunohistochemical, and real-time PCR methodology. We determined that the same low dose of the NOP antagonist [Nphe1]N/OFQ(1-13)NH2 delivered via the lateral ventricle diminishes both N/OFQ- and deprivation-induced feeding. This anorexigenic effect did not stem from aversive consequences, as the antagonist did not cause the development of a CTA. When [Nphe1]N/OFQ(1-13)NH2 was administered with LiCl, it moderately delayed extinction of the LiCl-induced CTA. Injection of LiCl + antagonist compared with LiCl alone generated an increase in c-Fos immunoreactivity in the central nucleus of the amygdala. The antagonist alone elevated Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, and central nucleus of the amygdala. Hypothalamic NOP mRNA levels were decreased during energy intake restriction induced by aversion, as well as in non-CTA rats food-restricted to match CTA-reduced consumption. Brain stem NOP was upregulated only in aversion. Prepro-N/OFQ mRNA showed a trend toward upregulation in restricted rats ( P = 0.068). We conclude that the N/OFQ system promotes feeding by affecting the need to replenish lacking calories and by reducing aversive responsiveness. It may belong to mechanisms that shift a balance between the drive to ingest energy and avoidance of potentially tainted food.
Temporally and spatially controllable gene expression and knockout in mouse urothelium
Authors: Zhou Haiping , Liu Yan , He Feng , Mo Lan , Sun Tung-Tien , Wu Xue-Ru
Published: April 2010

Urothelium that lines almost the entire urinary tract performs important functions and is prone to assaults by urinary microbials, metabolites, and carcinogens. To improve our understanding of urothelial physiology and disease pathogenesis, we sought to develop two novel transgenic systems, one that would allow inducible and urothelium-specific gene expression, and another that would allow inducible and urothelium-specific knockout. Toward this end, we combined the ability of the mouse uroplakin II promoter (mUPII) to drive urothelium-specific gene expression with a versatile tetracycline-mediated inducible system. We found that, when constructed under the control of mUPII, only a modified, reverse tetracycline trans-activator (rtTA-M2), but not its original version (rtTA), could efficiently trans-activate reporter gene expression in mouse urothelium on doxycycline (Dox) induction. The mUPII/rtTA-M2-inducible system retained its strict urothelial specificity, had no background activity in the absence of Dox, and responded rapidly to Dox administration. Using a reporter gene whose expression was secondarily controlled by histone remodeling, we were able to identify, colocalize with 5-bromo-2-deoxyuridine incorporation, and semiquantify newly divided urothelial cells. Finally, we established that, when combined with a Cre recombinase under the control of the tetracycline operon, the mUPII-driven rtTA-M2 could inducibly inactivate any gene of interest in mouse urothelium. The establishment of these two new transgenic mouse systems enables the manipulation of gene expression and/or inactivation in adult mouse urothelium at any given time, thus minimizing potential compensatory effects due to gene overexpression or loss and allowing more accurate modeling of urothelial diseases than previously reported constitutive systems.
Potassium secretion by voltage-gated potassium channel Kv1.3 in the rat kidney
Authors: Carrisoza-Gaytán Rolando , Salvador Carolina , Satlin Lisa M. , Liu Wen , Zavilowitz Beth , Bobadilla Norma A. , Trujillo Joyce , Escobar Laura I.
Published: April 2010

The fine regulation of Na+and K+transport takes place in the cortical distal nephron. It is well established that K+secretion occurs through apical K+channels: the ROMK and the Ca2+- and voltage-dependent maxi-K. Previously, we identified the voltage-gated Kv1.3 channel in the inner medulla of the rat kidney (Escobar LI, Martínez-Téllez JC, Salas M, Castilla SA, Carrisoza R, Tapia D, Vázquez M, Bargas J, Bolívar JJ. Am J Physiol Cell Physiol 286: C965–C974, 2004). To examine the role of Kv1.3 in the renal regulation of K+homeostasis, we characterized the effect of dietary K+on the molecular and functional expression of this channel. We performed real-time-PCR and immunoblot assays in kidneys from rats fed a control (CK; 1.2% wt/wt) or high-K+(HK; 10% wt/wt) diet for 5–15 days. Kv1.3 mRNA and protein expression did not change with HK in the whole kidney. However, dietary K+loading provoked a change in the cellular distribution of Kv1.3 from the cytoplasm to apical membranes. Immunolocalization of Kv1.3 detected the channel exclusively in the intercalated cells. We investigated whether Kv1.3 mediated K+transport in microperfused cortical collecting ducts (CCDs). The HK diet led to an increase in net K+transport from 7.4 ± 1.1 (CK) to 11.4 ± 1.0 (HK) pmol·min−1·mm−1. Luminal margatoxin, a specific blocker of Kv1.3, decreased net K+secretion in HK CCDs to 6.0 ± 1.6 pmol·min−1·mm−1. Our data provide the first evidence that Kv1.3 channels participate in K+secretion and that apical membrane localization of Kv1.3 is enhanced in the intercalated cells by dietary K+loading.
Subcutaneous Sarcoidosis during Pegylated Interferon Alfa and Ribavirin Treatment for Chronic Hepatitis C
Authors: Rodríguez-Lojo R. , Almagro M. , Barja J. M. , Piñeyro F. , Pérez-Varela L. , Del Pozo J. , Yebra-Pimentel M. T. , Fonseca E.
Published: April 2010

Interferon is used to treat hepatitis C virus infection and its cutaneous side effects are well known. Recently, interferon‐induced sarcoidosis has been reported. We report a new case of sarcoidosis during pegylated interferon alfa and ribavirin treatment with an unusual presentation in a woman with previous episodes of erythema nodusum and nodular vasculitis related to HCV.
Behavior of Carbon-Carbon Composite under Intense Heating
Authors: Palaninathan R.
Published: April 2010

This paper is concerned with modeling of ablation behavior of carbon-carbon composites used in hot spot areas of reentry space and hypersonic vehicles. Of the three modes of ablation (thermal, chemical and mechanical), the chemical (oxidation) is considered to influence the performance of the material. Aerodynamic heat flux need to be computed separately and is the input for this. The thermal field is obtained by 3D finite element method. Nonlinear transient thermal analysis is carried out, as the material properties are dependent on temperatures. Oxidation rates are computed using the analytical relations available in literature. The oxidation is divided into two regimes: reaction rate and diffusion rate controlled. Mainly the surface temperature controls the regime. The oxidation protected materials are considered by using the parameter “activation energy.” The variations of ambient temperature, pressure and oxygen concentration with altitude are taken into consideration. As the recession takes place, newer surfaces are exposed to aerodynamic heating. Numerical examples are presented to show the effects of: heat flux, altitude and oxidation protection on the recession characteristics. Change of regime from reaction to diffusion rate control depends on parameters such as flow velocity and altitude. The latter has significant influence on ablation rate.
Caries Detection Methods Based on Changes in Optical Properties between Healthy and Carious Tissue
Authors: Karlsson Lena
Published: April 2010

A conservative, noninvasive or minimally invasive approach to clinical management of dental caries requires diagnostic techniques capable of detecting and quantifying lesions at an early stage, when progression can be arrested or reversed. Objective evidence of initiation of the disease can be detected in the form of distinct changes in the optical properties of the affected tooth structure. Caries detection methods based on changes in a specific optical property are collectively referred to as optically based methods. This paper presents a simple overview of the feasibility of three such technologies for quantitative or semiquantitative assessment of caries lesions. Two of the techniques are well-established: quantitative light-induced fluorescence, which is used primarily in caries research, and laser-induced fluorescence, a commercially available method used in clinical dental practice. The third technique, based on near-infrared transillumination of dental enamel is in the developmental stages.
The Evaluation of the Vector System in Removal of Carious Tissue
Authors: Yildirim Mine , Seymen Figen , Keklikoglu Nurullah
Published: April 2010

The aim of this study was to evaluate the Vector system in comparison to the conventional technique in cavity preparation. Four extracted primary teeth with no restorations and similar fissure carious lesions and four permanent teeth extracted for orthodontic reasons were used. Class I preparations were made provided that the caries depth remained within the dentin limits. Two teeth were treated with an aerator, the other two had carious tissue removed with the Vector system. Prepared cavities were evaluated with scanning electron microscopy for the surface roughness of the dentine and enamel and for the carious tissue removal efficiency. This pilot study determined that it is possible to remove carious tissue and perform cavity preparation with the Vector system. According to this preliminary evaluation of surface quality, a cavity prepared with the Vector treatment system, allows for a slicker floor, and a more regular enamel-dentine line than that prepared with an aerator. However, the Vector system requires a longer treatment time which we believe may be a negative point, especially for young patients.
Detection of EBV, HBV, HCV, HIV-1, HTLV-I and -II, and SMRV in Human and Other Primate Cell Lines
Authors: Uphoff Cord C. , Denkmann Sabine A. , Steube Klaus G. , Drexler Hans G.
Published: April 2010

The high prevalence of contaminated cell cultures suggests that viral contaminations might be distributed among cultures. We investigated more than 460 primate cell lines for Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus type 1 (HIV-1), human T-cell leukemia/lymphoma virus I and II (HTLV-I/-II), and squirrel monkey retrovirus (SMRV) infections for risk assessment. None of the cell lines were infected with HCV, HIV-1, or HTLV-I/-II. However, one cell line displayed reverse transcriptase activity. Thirty-nine cell lines harbored EBV DNA sequences. Studies on the lytic phase of EBV revealed that five cell lines produce EBV particles and six further cell lines produced EBV upon stimulation. One cell line contained an integrated HBV genome fragment but showed no virus production. Six cell lines were SMRV-infected. Newly established cell lines should be tested for EBV infections to detect B-lymphoblastoid cell lines (B-LCL). B-LCLs established with EBV from cell line B95-8 should be tested for SMRV infections.
Selective Visualization of Cyclooxygenase-2 in Inflammation and Cancer by Targeted Fluorescent Imaging Agents
Authors: Uddin Md. Jashim , Crews Brenda C. , Blobaum Anna L. , Kingsley Philip J. , Gorden D. Lee , McIntyre J. Oliver , Matrisian Lynn M. , Subbaramaiah Kotha , Dannenberg Andrew J. , Piston David W. , Marnett Lawrence J.
Published: April 2010

Effective diagnosis of inflammation and cancer by molecular imaging is challenging because of interference from nonselective accumulation of the contrast agents in normal tissues. Here, we report a series of novel fluorescence imaging agents that efficiently target cyclooxygenase-2 (COX-2), which is normally absent from cells, but is found at high levels in inflammatory lesions and in many premalignant and malignant tumors. After either i.p. or i.v. injection, these reagents become highly enriched in inflamed or tumor tissue compared with normal tissue and this accumulation provides sufficient signal for in vivo fluorescence imaging. Further, we show that only the intact parent compound is found in the region of interest. COX-2–specific delivery was unambiguously confirmed using animals bearing targeted deletions of COX-2 and by blocking the COX-2 active site with high-affinity inhibitors in both in vitro and in vivo models. Because of their high specificity, contrast, and detectability, these fluorocoxibs are ideal candidates for detection of inflammatory lesions or early-stage COX-2–expressing human cancers, such as those in the esophagus, oropharynx, and colon. Cancer Res; 70(9); 3618–27. ©2010 AACR.
Sustained Small Interfering RNA Delivery by Mesoporous Silicon Particles
Authors: Tanaka Takemi , Mangala Lingegowda S. , Vivas-Mejia Pablo E. , Nieves-Alicea René , Mann Aman P. , Mora Edna , Han Hee-Dong , Shahzad Mian M.K. , Liu Xuewu , Bhavane Rohan , Gu Jianhua , Fakhoury Jean R. , Chiappini Ciro , Lu Chunhua , Matsuo Koji , Godin Biana , Stone Rebecca L. , Nick Alpa M. , Lopez-Berestein Gabriel , Sood Anil K. , Ferrari Mauro
Published: April 2010

RNA interference (RNAi) is a powerful approach for silencing genes associated with a variety of pathologic conditions; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained systemic delivery. Here, we report on a novel approach to overcome these limitations using a multistage vector composed of mesoporous silicon particles (stage 1 microparticles, S1MP) loaded with neutral nanoliposomes (dioleoyl phosphatidylcholine, DOPC) containing small interfering RNA (siRNA) targeted against the EphA2 oncoprotein, which is overexpressed in most cancers, including ovarian. Our delivery methods resulted in sustained EphA2 gene silencing for at least 3 weeks in two independent orthotopic mouse models of ovarian cancer following a single i.v. administration of S1MP loaded with EphA2-siRNA-DOPC. Furthermore, a single administration of S1MP loaded with-EphA2-siRNA-DOPC substantially reduced tumor burden, angiogenesis, and cell proliferation compared with a noncoding control siRNA alone (SKOV3ip1, 54%; HeyA8, 57%), with no significant changes in serum chemistries or in proinflammatory cytokines. In summary, we have provided the first in vivo therapeutic validation of a novel, multistage siRNA delivery system for sustained gene silencing with broad applicability to pathologies beyond ovarian neoplasms. Cancer Res; 70(9); 3687–96. ©2010 AACR.
Estrogen Receptor Mutations and Changes in Downstream Gene Expression and Signaling
Authors: Barone Ines , Brusco Lauren , Fuqua Suzanne A.W.
Published: April 2010

Estrogens play a crucial role in regulating the growth and differentiation of breast cancers, with approximately two thirds of all breast tumors expressing the estrogen receptor alpha (ERα). Therefore, therapeutic strategies directed at inhibiting the action of ERα by using anti-estrogens such as tamoxifen, or reducing estrogens levels by using aromatase inhibitors, such as letrozole, anastrozole, or exemestane, are the standard treatments offered to women with ERα-positive cancer. However, not all patients respond to endocrine therapies (termed de novo resistance), and a large number of patients who do respond will eventually develop disease progression or recurrence while on therapy (acquired resistance). Recently, variant forms of the receptor have been identified owing to alternative splicing or gene mutation. This article reviews these variant receptors and their clinical relevance in resistance to endocrine therapy, by addressing their molecular cross-talk with growth factor receptors and signaling components. Understanding the complexity of receptor-mediated signaling has promise for new combined therapeutic options that focus on more efficient blockade of receptor cross-talk. Clin Cancer Res; 16(10); 2702–8. ©2010 AACR.
Validation of Emergency and Final Diagnosis Coding in Transient Ischemic Attack: South Western Sydney Transient Ischemic Attack Study
Authors: Ghia Darshan , Thomas Peter R. , Cordato Dennis J. , Worthington John M. , Cappelen-Smith Cecilia , Griffith Neil , Hanna Ibrahim , Hodgkinson Suzanne J. , McDougall Alan , Beran Roy G.
Published: April 2010

Background: It is important to establish the validity of diagnostic coding in administrative datasets used in stroke and transient ischemic attack (TIA) research. This study examines the accuracy of emergency department (ED) TIA diagnosis and final diagnostic coding after hospital admission. Methods: Using administrative datasets, we identified all patients with an ED TIA diagnosis (435.9; ICD-9) admitted to Liverpool Hospital from January 2003 to December 2007. ED and hospital admission records were matched and final diagnosis codes (ICD-10-AM) recorded. All records were expertly reviewed to determine coding validity. Results: 570 patients were admitted with an ED TIA diagnosis. According to ICD-10-AM coding, 46% had TIA, 29% stroke and 25% TIA mimic diagnoses. Expert review determined final diagnoses of TIA in 51.4%, stroke in 26.1% and TIA mimic in 22.5% of the patients. The positive predictive value of a final TIA diagnosis (ICD-10-AM) was 88.2% when subjected to expert review. TIA mimic disorders diagnosed after admission included serious conditions. Conclusions: Half of the emergency diagnoses retained a TIA diagnosis after hospital admission. In the setting of neurological admission there were small percentage differences between coded final diagnosis for TIA, stroke and mimic and diagnoses at expert review. Admission of ED TIA cases permitted identification of TIA mimics with serious conditions requiring non-TIA management.
Everyday Cognitive Failure in Sarcoidosis: The Prevalence and the Effect of Anti-TNF-α Treatment
Authors: Elfferich Marjon D. , Nelemans Patty J. , Ponds Rudolf W. , De Vries Jolanda , Wijnen Petal A. , Drent Marjolein
Published: April 2010

Background: Cognitive symptoms, such as concentration problems, are frequently recorded by sarcoidosis patients. Objectives: The aim of this study was to assess the prevalence of perceived everyday cognitive failure in sarcoidosis patients and healthy controls. Furthermore, the effect of treatment on cognitive functioning was examined. Methods: The study included 343 sarcoidosis patients (44.6% females; age 49.3 ± 11.0 years). They completed the Cognitive Failure Questionnaire (CFQ) and Fatigue Assessment Scale (FAS) at baseline and the 6-month follow-up to evaluate the effect of treatment on cognitive functioning. The control group consisted of 343 age- and sex-matched healthy controls. Results: The mean CFQ score was significantly higher in sarcoidosis patients (37.3 ± 16.1) compared with the controls (31.3 ± 10.1; p < 0.0001).A high CFQ sore (≧43) was found in 35.0% of the patients and only 14.3% of the controls. No relation with disease severity and duration, or disease location was found. The proportion of patients receiving treatment did not differ among the groups with high and normal CFQ score. At the 6-month follow-up, only patients recently treated with anti-TNF-α therapy (n = 42) demonstrated a significant improvement in the CFQ score (Δ –7.07 ± 7.23) compared with the untreated patients (Δ –0.08 ± 9.35) and patients treated with prednisone with or without methotrexate (Δ 1.67 ± 9.22; p < 0.0001). After adjustment for the concomitant decrease in fatigue, the effect of anti-TNF-α therapy remained high and significant. Conclusions: Subjective cognitive failure is a substantial problem in sarcoidosis patients regardless of disease severity. Anti-TNF-α therapy had a positive effect on cognition, fatigue and other symptoms of sarcoidosis.
Antagonism of P2Y12 or GPIIb/IIIa receptors reduces platelet-mediated myocardial injury after ischaemia and reperfusion in isolated rat hearts
Authors: Barrabés José A. , Inserte Javier , Mirabet Maribel , Quiroga Adoración , Hernando Víctor , Figueras Jaume , Garcia-Dorado David
Published: April 2010

Platelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. This study aimed to investigate whether platelets from patients with AMI increase myocardial injury after ischaemia and reperfusion in isolated rat hearts and the modification of this effect by the P2Y12 receptor antagonist cangrelor and the glycoprotein IIb/IIIa receptor blocker abciximab. Isolated rat hearts were subjected to 40 minutes of global ischaemia and 60 minutes of reperfusion. Hearts (four simultaneous experiments per patient) were infused with platelets from nine AMI patients (seven thrombolysed, all on aspirin), untreated or incubated with 10 μM cangrelor or 5 μg/ml abciximab. Control experiments were performed using platelets from healthy volunteers and platelet-poor plasma. P-selectin expression on isolated platelets was higher in AMI patients than in controls and was not modified by the treatments. Control platelets or platelet-poor plasma did mild or no harm. In contrast, platelets from AMI patients significantly augmented myocardial injury, as demonstrated by worse left ventricular (LV) developed pressure, higher maximal LV end-diastolic pressure and coronary resistance, and greater lactate dehydrogenase release and infarct size. Both cangrelor and abciximab greatly attenuated these effects. In conclusion, activated platelets from AMI patients increase myocardial injury after ischaemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment might reduce infarct size by direct effects on reperfused myocardium in these patients.
In vitro factor XIII supplementation increases clot firmness in Rotation Thromboelastometry (ROTEM®)
Authors: Asmis Lars , Seifert Burkhardt , Spahn Donat , Theusinger Oliver , Baulig Werner
Published: April 2010

Factor XIII (F XIII) is an essential parameter for final clot stability. The purpose of this study was to determine the impact of the addition of factor (F)XIII on clot stability as assessed by Rotation Thromboelastometry (ROTEM®). In 90 intensive care patients ROTEM® measurements were performed after in vitro addition of F XIII 0.32 IU, 0.63 IU, 1.25 IU and compared to diluent controls (DC; aqua injectabile) resulting in approximate F XIII concentrations of 150, 300 and 600%. Baseline measurements without any additions were also performed. The following ROTEM® parameters were measured in FIBTEM and EXTEM tests: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), maximum lysis (ML), maximum clot elasticity (MCE) and α-angle (αA). Additionally, laboratory values for FXIII, fibrinogen (FBG), platelets and haematocrit were contemporaneously determined. In the perioperative patient population mean FBG concentration was elevated at 5.2 g/l and mean FXIII concentration was low at 62%. The addition of FXIII led to a FBG concentration-dependent increase in MCF both in FIBTEM and EXTEM. Mean increases in MCF (FXIII vs. DC) of approximately 7 mm and 6 mm were observed in FIBTEM and EXTEM, respectively. F XIII addition also led to decreased CFT, increased αA, and reduced ML in FIBTEM and EXTEM. In vitro supplementation of FXIII to supraphysiologic levels increases maximum clot firmness, accelerates clot formation and increases clot stability in EXTEM and FIBTEM as assayed by ROTEM® in perioperative patients with high fibrinogen and low FXIII levels.
Global Administrative Law Perspective of the WTO Aid for Trade Initiative
Authors: Illy Ousseni , Marceau Gabrielle
Published: April 2010

The emerging Global Administrative Law (GAL) study has brought into the legal frontlines the need to hold global governance bodies more accountable for their rulings and activities, and how these institutions are adapting their actions to better respond to new global challenges as their legitimacy depends on their effectiveness in coping with them. The legitimacy challenge has become a pressing issue, forcing international organizations to open up their decision-making processes and to set up review mechanisms to oversee their actions. The recent WTO Aid for Trade (AFT) Initiative belongs to this new category of global action/forums that want to respond to legitimacy and accountability challenges. This innovative movement has provided the WTO Director General with the responsibility to launch and institutionalize an initiative to allow poorer countries to derive more benefit from the Multilateral Trading System. It has brought together a wide range of stakeholders including international aid-donor states, beneficiary states, international financial and development institutions, regional banks and regional institutions, private sector, NGOs etc. to discuss and shape the best way to achieve this aim. This article tries to assess the AFT Initiative against the principles advocated by GAL, in particular those related to participation, transparency, accountability and review.
Emergency Action by the WTO Director-General: Global Administrative Law and the WTO's Initial Response to the 2008–09 Financial Crisis
Authors: Berman Ayelet , Pauwelyn Joost
Published: April 2010

The WTO's initial reaction to the 2008–2009 financial crisis was taken mainly by its managerial arm, that is, by the Director-General (DG) and the Secretariat and not by its legislative or judicial bodies. This is a novelty for the WTO and illustrates the emergence, even at the otherwise hard-law WTO, of informal administrative actions that go beyond the traditional member-dominated WTO. The actions were in two areas: The DG convened trade finance expert meetings with other organizations and private banks, and the Secretariat prepared reports on trade-related measures enacted across the globe in response to the crisis. The article examines these actions in light of certain concepts and principles of the GAL project. Overall, the Director-General was sensitive in his actions to GAL principles.
Commercial Density, Residential Concentration, and Crime: Land Use Patterns and Violence in Neighborhood Context
Authors: Browning Christopher R. , Byron Reginald A. , Calder Catherine A. , Krivo Lauren J. , Kwan Mei-Po , Lee Jae-Yong , Peterson Ruth D.
Published: April 2010

Drawing on Jacobs’s (1961) and Taylor’s (1988) discussions of the social control implications of mixed land use, the authors explore the link between commercial and residential density and violent crime in urban neighborhoods. Using crime, census, and tax parcel data for Columbus, Ohio, the authors find evidence of a curvilinear association between commercial and residential density and both homicide and aggravated assault, consistent with Jacobs’s expectations. At low levels, increasing commercial and residential density is positively associated with homicide and aggravated assault. Beyond a threshold, however, increasing commercial and residential density serves to reduce the likelihood of both outcomes. In contrast, the association between commercial and residential density and robbery rates is positive and linear. The implications of these findings for understanding the sources of informal social control in urban neighborhoods are discussed.
The Politics of Housing Consumption: Renters as Flawed Consumers on a Master Planned Estate
Authors: Cheshire Lynda , Walters Peter , Rosenblatt Ted
Published: April 2010

Master planned estates offer package dreams of homeownership to those wanting to live among others who share their lifestyle aspirations. Yet we show in this paper how divisions can arise between housing tenure types, with owner-occupiers constructing private rental tenants as a problem. Extending Bauman’s concept of the flawed consumer using Rose’s writings on ethopolitics, we show how renters are viewed as failing in three domains of social life: aesthetics, ethics and community by undermining the aesthetic value of the neighbourhood and by failing to demonstrate an ethic of care for themselves and others. As a result, the homeowners in this study try to avoid living among rental properties and are disappointed to find that, contrary to expectations, moving to a master planned estate does not guarantee this.
National Context and Atypical Employment
Authors: Hevenstone Debra
Published: April 2010

This article takes a macro-approach, examining country-level determinants of three types of atypical employment (fixed-term, part-time and self-employment) in 30 developed countries. Support is found for three hypotheses: atypical work arrangements are more prevalent (1) when there is a strong entrepreneurial culture, (2) when there are legal constraints on firms’ ability to hire and fire workers and (3) when economic constraints force workers to accept atypical employment. The article also qualitatively examines three countries’ legislative, judicial and economic histories with respect to atypical work, contrasting the three histories with the quantitative analysis.
Class Inequalities in Political Participation and the ‘Death of Class’ Debate
Authors: Caínzos Miguel , Voces Carmen
Published: April 2010

The aim of this article is to offer an empirical contribution to the debate on the political significance of class, and especially the relationship between class position and political participation. The ‘death of class’ debate has primarily addressed only one aspect of politics — voting. The perspective offered here widens the scope of analysis to include the main forms of political action available to citizens in modern democracies. In this article, a comparative cross-national approach is adopted, using data on 20 European countries that are included in the first wave of the European Social Survey. Using log-linear models as a descriptive device, the article identifies a basic pattern of association between class and participation, points out the main national deviations from that pattern and makes a comparative assessment of the relative magnitude of overall levels of class inequalities in participation in different forms of political activity. The results bear out the continuing relevance of class as a source of differentiation of political behaviour and tend to confirm previous research regarding the validity of empirical generalizations on class patterns of political participation.