bluuebunny/crossref_metadata_2025 huggingface dataset:
d‐Serine Regulates Proliferation and Neuronal Differentiation of Neural Stem Cells from Postnatal Mouse Forebrain
Authors: Huang Xu , Kong Hui , Tang Mi , Lu Ming , Ding Jian‐Hua , Hu Gang
Published: January 2012

SUMMARY  Background and purpose:
d‐Serine, the endogenous co‐agonist of N‐methyl‐d‐aspartate (NMdA) receptors, has been recognized as an important gliotransmitter in the mammalian brain. d‐serine has been shown to prevent psychostimulant‐induced decrease in hippocampal neurogenesis. However, the mechanism whereby d‐serine regulates neurogenesis has not been fully characterized. Therefore, this study was designed to investigate the impacts of d‐serine on the proliferation, migration, and differentiation of primary cultured neural stem cells (NSCs). Methods and results: Immunohistochemistry analysis revealed NSCs expressed d‐serine as well as serine racemase (SR). Degradation of endogenous d‐serine with d‐amino acid oxidase (dAAO) significantly inhibited the proliferation and neuronal differentiation of NSCs, but failed to affect their radial migration. Reversely, addition of exogenous d‐serine did not affect the proliferation and migration of NSCs, but promoted NSC differentiation into neurons. Furthermore, dAAO could suppress the amplitude of glutamate‐induced Ca2+ transient, and thereby, inhibited the phosphorylation of glycogen synthase kinase3β (GSK3β), extracellular signal‐regulated kinases1/2 (ERK1/2), and cAMP‐responsive element‐binding protein (CREB). Conclusions: Our findings demonstrate for the first time that NSCs can synthesize d‐serine and, thereby, promote themselves proliferation and neuronal differentiation, which may afford a novel therapeutic strategy for the neurological disorders that require nerve cell replenishment, such as neurodegenerative diseases and stroke.
The Case for Decoupled Armed Interventions
Authors: Etzioni Amitai
Published: January 2012

This article suggests that if the humanitarian goals of armed interventions are decoupled from coerced regime change and nation building, they can be carried out effectively and at rather low costs. In addition, the standard for justifying a humanitarian intervention must be set at a high level (to be specified below). We shall see that this high level is justified by strong normative reasons and not merely prudential ones. The thesis for narrowly crafted armed humanitarian interventions is supported in the following pages by showing that a mixture of idealism and hubris drives the West to assume that it can achieve much more, and that its repeated failure to accomplish these expansive goals is leading to calls to avoid armed humanitarian interventions—including those missions whose normative standing is strong and which can be carried out effectively. The observation that nations can employ non lethal (normative and economic) means to promote human rights and democracy further supports the thesis that the use of force should be reserved to large scale saving of life and not to be allowed to morph into coerced regime change, not to mention futile attempts at nation building.
Retroperitoneal approach for laparoscopic nephroureterectomy with stripping technique: Extracorporeal ligation of ureter and ureteral catheter
Authors: Nakamura K. , Nagata D. , Kajikawa K , Kobayashi I , Zennami K , Nishikawa G , Yoshizawa T , Tobiume M , Aoki S , Yamada Y , Sumitomo M
Published: January 2012

Introduction

The pluck and stripping techniques are used for lower ureter management in renal pelvic cancer patients. Herein, we report our experience of extracorporeal ligation of the ureter and the ureteral catheter through the trocar port, which differs from conventional laparoscopic ligation in the retroperitoneal space. This technique was selected to reduce the time needed for ureter management using the stripping technique and to provide secure ligation.

Materials and Surgical Technique

We performed this stripping technique in patients with T1 and T2 stage renal pelvic cancer without imaging‐evident lymph node metastasis. After transurethrally placing a ureteral catheter, we resected the circumference of the ureteral orifice. After laparoscopic nephrectomy via a retroperitoneal approach, the ureteral catheter and distal ureter were ligated extracorporeally. The catheter was pulled to invaginate the ureter so it could then be pulled through the external urethral orifice.

Discussion

This technique of extracorporeal ligation ensures more a secure ligation of the ureter and ureteral catheter. This modified stripping technique does not require lower ureter management with laparotomy, and it is also useful in shortening the operative time. This method is effective for relatively early stage renal pelvic cancer.
Advancing Theory in Entrepreneurship from the Lens of Operations Management
Authors: Phan Phillip , Chambers Chester
Published: January 2012

Early writings in economics describe the entrepreneur's role in terms of bearing the uncertainty inherent in new undertakings. Much of the research published in the pages of Production and Operations Management deals with management under uncertainty. The shared concerns over the impacts of multiple types of uncertainty suggest that research on Operations Management (OM) can play a role in the development of theory in entrepreneurship. We discuss aspects of such a role from two perspectives. First, we consider several topics in the OM literature that have clear applications or parallels in entrepreneurship. These topics include innovation, the management of technology, new product development, flexibility, and hedging strategies. Understanding these topical connections should aid in the development of tools and applications central to the practice of entrepreneurship. On another level, when we consider how the approaches to many of these topics in OM are grounded in theory adapted from Operations Research and Economics we argue that these same roots can be used as starting points for the development of theory in entrepreneurship. As examples, we will argue that the theoretical bases supporting robust optimization, stochastic dynamic programming, and even Total Quality Management can also serve as foundations of theories about the roles, practice, and behaviors of entrepreneurs.
Discerning Reported Suicide Attempts Within a Youthful Offender Population
Authors: Mallett Christopher , De Rigne Lea A. , Quinn Linda , Stoddard‐Dare Patricia
Published: January 2012

With suicide being the third leading cause of death among young people, early identification of risk is critical, particularly for those involved with the juvenile courts. In this study of court‐involved youth (N = 433) in two Midwest counties, logistic regression analysis identified some expected and unexpected findings of important demographic, educational, mental health, child welfare, and juvenile court‐related variables that were linked to reported suicide attempts. Some of the expected suicide attempt risk factors for these youth included prior psychiatric hospitalization and related mental health services, residential placement, and diagnoses of depression and alcohol dependence. However, the most unexpected finding was that a court disposition to shelter care (group home) was related to a nearly tenfold increased risk in reported suicide attempt. These findings are of importance to families, mental health professionals, and juvenile court personnel to identify those youth who are most at risk and subsequently provide appropriate interventions to prevent such outcomes.
Inhibition by chlorpromazine of the effects of dopamine on the dog kidney
Authors: Brotzu Giovanni
Published: January 2012

Dopamine-induced vasodilatation in the renal artery of the dog is reversed by chlorpromazine while the vasodilatation produced by isoprenaline is not. Pronethalol has the entirely opposite actions on this preparation. The infusion of dopamine into the renal artery enhances the kidney output of water, sodium, potassium and urea. These effects are also reversed by chlorpromazine.
The effects of some tetracyclines on synchronously growing cultures of Escherichia coli B/r
Authors: Collett John H , Collett Catherine , Martin Alfred N , Cammarata Arthur
Published: January 2012

Samples of synchronously growing cultures of Escherichia coli B/r removed at predetermined time intervals after synchronization were added to solutions containing bactericidal concentrations of tetra-cycline. Three active antibacterials, 7-nitro-6-demethyl-6-deoxytetracycline, 9-amino-6-demethyl-6-deoxytetracycline and 6-demethyl-6-deoxytetracycline, and one inactive compound, 7-chloroisotetra-cycline, were studied. Survival curves for the active agents, determined using samples of culture differing in age, were of constant slope for a given tetracycline. It is concluded that interruption of protein synthesis is the primary mode of action at bactericidal concentrations of tetracyclines, the same process as has been established for the action of the tetracyclines at the lower bacteriostatic concentrations.
The preparation and intravenous anaesthetic activity of tetrahydrofuran-3-ols
Authors: Bamford D G , Biggs D F , Cuthbert M F , Grant H N , Lee G E , Pulsford D W , Wragg W R
Published: January 2012

A number of tetrahydrofuran-3-ols have been prepared and examined for intravenous anaesthetic activity. The compounds studied had low intrinsic anaesthetic activity and there was an inverse relation between anaesthetic activity or toxicity and solubility in water. It was considered unlikely that compounds comparable in activity to thiopentone or methohexitone would be found in this series.
Experimental and Modeling Studies of the Oxidation of Surrogate Bio-Aviation Fuels
Authors: Shafagh Ida , Hughes Kevin J. , Catalanotti Elena , Liu Zhen , Pourkashanian Mohamed , Wilson Chris W.
Published: January 2012

Jet fuels currently in use in the aviation industry are exclusively kerosene-based. However, potential problems regarding security of supply, climate change, and increasing cost are becoming more significant, exacerbated by the rapidly growing demand from the aviation sector. Biofuels are considered one of the most suitable alternatives to petrochemical-based fuels in the aviation industry in the short to medium term, since blends of biofuel and kerosene provide a good balance of properties currently required from an aviation fuel. Experimental studies at a variety of stoichiometries using a flat flame burner with kerosene and kerosene/biofuel blends have been performed with product analysis by gas sampling and laser-induced fluorescence detection of OH, CO, and CO2. These studies have been complemented by modeling using the PREMIX module of Chemkin to provide insights into and to validate combined models describing the oxidation chemistry of surrogate fuels depicting kerosene, fatty acid methyl ester biofuels, and Fischer-Tropsch derived fuels. Sensitivity analysis has identified important reactions within these schemes, which, where appropriate, have been investigated by molecular modeling techniques available within Gaussian 03.
Novel Natural Transdermal Otoliths/Collagen/Bacterial Cellulose Patch for Osteoporosis Treatment
Authors: de Olyveira Gabriel Molina , Costa Ligia Maria Manzine , Góis Plácia Barreto Prata , Basmaji Pierre , Xavier Filho Lauro
Published: January 2012

In the present work, we report the novel natural transdermal otoliths/collagen/bacterial cellulose patch for osteoporosis treatment. This biomaterial is an osteoinductor, or be, stimulates the bone regeneration, enabling bigger migration of the cells for formation of the bone fabric. Otolith is a typical biomaterial that is composed of calcium carbonate and organic matrix. Otoliths are calcareous concrescences present in the inner ear of fishes. Since they are rich in minerals, they are considered essential to the bone mineralization process on a protein matrix (otolin). The objective in this study was to analyze the regeneration capacity of bone defects treated with otoliths network preparation. Collagen and nano-otoliths influences in bacterial cellulose was analyzed using transmission infrared spectroscopy (FTIR). In vivo analysis shows bone surface tissue with high regularity, higher osteoblast activity, and osteo-reabsorption activities areas. These results indicated that the transdermal permeation of otollith using this patch system was sufficient for the treatment of bone diseases. These findings indicate that our novel transdermal delivery system for otolith/collagen/bacterial cellulose is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases.
Selection of Climatic Design Points for Gas Turbine Power Augmentation
Authors: Chaker Mustapha , Meher-Homji Cyrus B.
Published: January 2012

There is a widespread interest in the application of gas turbine power augmentation technologies such as evaporative cooling and mechanical chilling in the mechanical drive and power generation markets. Very often, the selection of the design point is based on the use of American Society of Heating and Refrigeration Engineers (ASHRAE) data or a design point that is in the basis of design for the project. This approach can be detrimental and can result in a non optimal solution. In order to evaluate the benefits of power augmentation, users can use locally collected weather data, or recorded hourly bin data set from databases such as typical meteorological year (TMY), engineering weather data (EWD), and integrated weather surface (IWS). This paper will cover a suggested approach for the analysis of climatic data for power augmentation applications and show how the selection of the design point can impact performance. The final selection of the design point depends on the specific application, the revenues generated and installation costs. To the authors’ knowledge, this is the first attempt to treat this topic in a structured analytical manner by comparing available database information with actual climatic conditions.
Wind Turbine Gearbox Fault Detection Using Multiple Sensors With Features Level Data Fusion
Authors: Lu Y. , Tang J. , Luo H.
Published: January 2012

Fault detection in complex mechanical systems such as wind turbine gearboxes remains challenging, even with the recently significant advancement of sensing and signal processing technologies. As first-principle models of gearboxes capable of reflecting response details for health monitoring purpose are difficult to obtain, data-driven approaches are often adopted for fault detection, identification or classification. In this paper, we propose a data-driven framework that combines information from multiple sensors and fundamental physics of the gearbox. Time domain vibration and acoustic emission signals are collected from a gearbox dynamics testbed, where both healthy and faulty gears with different fault conditions are tested. To deal with the nonstationary nature of the wind turbine operation, a harmonic wavelet based method is utilized to extract the time-frequency features in the signals. This new framework features the employment of the tachometer readings and gear meshing relationships to develop a speed profile masking technique. The time-frequency wavelet features are highlighted by applying the mask we construct. Those highlighted features from multiple accelerometers and microphones are then fused together through a statistical weighting approach based on principal component analysis. Using the highlighted and fused features, we demonstrate that different gear faults can be effectively detected and identified.
Force Feedback Control for Active Stabilization of Synchronous Whirl Orbits in Rotor Systems With Nonlinear Stiffness Elements
Authors: Cole M. O. T. , Chamroon C. , Ngamprapasom P.
Published: January 2012

Synchronous vibration in rotor systems having bearings, seals, or other elements with nonlinear stiffness characteristics is prone to amplitude jump when operating close to critical speeds as there may be two or more possible whirl motions for a given unbalance condition. This paper describes research on how active control techniques may eliminate this potentially undesirable behavior. A control scheme based on feedback of rotor-stator interaction forces is considered. Model-based conditions for stability of low amplitude whirl, derived using Lyapunov’s direct method, are used to synthesize controller gains. Subsidiary requirements for existence of a static feedback control law that can achieve stabilization are also explained. An experimental validation is undertaken on a flexible rotor test rig where nonlinear rotor-stator contact interaction can occur across a small radial clearance in one transverse plane. A single radial active magnetic bearing is used to apply control forces in a separate transverse plane. The experiments confirm the conditions under which static feedback of the measured interaction force can prevent degenerate whirl responses such that a low amplitude contact-free orbit is the only possible steady-state response. The gain synthesis method leads to controllers that are physically realizable and can eliminate amplitude jump over a range of running speeds.
Foot Placement and Balance in 3D
Authors: Millard Matthew , McPhee John , Kubica Eric
Published: January 2012

Humans use carefully chosen step locations to restore their balance during locomotion and in response to perturbations. Understanding the relationship between foot placement and balance restoration is key to developing useful dynamic human balance diagnostic tests and balance rehabilitation treatments. The link between foot placement and balance restoration is studied in this paper using a simplified monopedal model that has a circular foot, coined the Euler pendulum. The Euler pendulum provides a convenient method of studying the stability properties of three-dimensional (3D) bipedal systems without the burden of large system equations typical of multibody systems. The Euler pendulum has unstable regions of its state-space that can be made to transition to a statically stable region using an appropriate foot placement location prior to contacting the ground. The planar foot placement estimator (FPE) method developed by Wight et al. is extended in this work in order to find foot placement locations in 3D to balance the 3D Euler pendulum. Preliminary experimental data shows that the 3D foot placement estimator (3DFPE) location corresponds very well with human foot placement during walking, gait termination, and when landing from a jump. In addition, a sensitivity analysis revealed that the assumptions of the 3DFPE are reasonable for human movement. Metrics for bipedal instability and balance performance suggested in this work could be of practical significance for health care professionals.
Nanomedicine in Cardiovascular Diseases: Emerging Diagnostic and Therapeutic Potential
Authors: Sureddi Ravi , Mehta Jawahar L.
Published: January 2012

Cardiovascular diseases, especially myocardial ischemia, have been a leading cause of death worldwide for several decades. Despite major advances in the diagnostic and therapeutic modalities available for the clinical management of patients with cardiovascular disease, significant limitations remain. The use of very small molecular particles has recently emerged as a novel technique for diagnostic imaging and treatment of a variety of disease processes and can be broadly classified under the category Nanomedicine. Many diagnostic and therapeutic modalities based on these small molecular particles have become part of routine clinical practice, such as liposomal amphotericin B for the treatment of fungal infections and iron nanoparticles for imaging liver tumors. In this review, we discuss the potential applications of nanomedicine in the management of cardiovascular diseases.
Rotational Stiffness of Football Shoes Influences Talus Motion during External Rotation of the Foot
Authors: Wei Feng , Meyer Eric G. , Braman Jerrod E. , Powell John W. , Haut Roger C.
Published: January 2012

Shoe-surface interface characteristics have been implicated in the high incidence of ankle injuries suffered by athletes. Yet, the differences in rotational stiffness among shoes may also influence injury risk. It was hypothesized that shoes with different rotational stiffness will generate different patterns of ankle ligament strain. Four football shoe designs were tested and compared in terms of rotational stiffness. Twelve (six pairs) male cadaveric lower extremity limbs were externally rotated 30 deg using two selected football shoe designs, i.e., a flexible shoe and a rigid shoe. Motion capture was performed to track the movement of the talus with a reflective marker array screwed into the bone. A computational ankle model was utilized to input talus motions for the estimation of ankle ligament strains. At 30 deg of rotation, the rigid shoe generated higher ankle joint torque at 46.2 ± 9.3 Nm than the flexible shoe at 35.4 ± 5.7 Nm. While talus rotation was greater in the rigid shoe (15.9 ± 1.6 deg versus 12.1 ± 1.0 deg), the flexible shoe generated more talus eversion (5.6 ± 1.5 deg versus 1.2± 0.8 deg). While these talus motions resulted in the same level of anterior deltoid ligament strain (approxiamtely 5%) between shoes, there was a significant increase of anterior tibiofibular ligament strain (4.5± 0.4% versus 2.3 ± 0.3%) for the flexible versus more rigid shoe design. The flexible shoe may provide less restraint to the subtalar and transverse tarsal joints, resulting in more eversion but less axial rotation of the talus during foot/shoe rotation. The increase of strain in the anterior tibiofibular ligament may have been largely due to the increased level of talus eversion documented for the flexible shoe. There may be a direct correlation of ankle joint torque with axial talus rotation, and an inverse relationship between torque and talus eversion. The study may provide some insight into relationships between shoe design and ankle ligament strain patterns. In future studies, these data may be useful in characterizing shoe design parameters and balancing potential ankle injury risks with player performance.
Multiuser interference cancellation in time-varying channels
Authors: Cho S. E. , Song H. C. , Hodgkiss W. S.
Published: January 2012

In this letter, an adaptive time-reversal multichannel combiner is embedded within an iterative successive interference cancellation receiver. With the addition of matching pursuit, a sparse channel estimation technique, the combined receiver is shown to provide both temporal interference cancellation as well as spatial interference suppression in decoding simultaneous transmissions from separate users in a time-varying underwater acoustic environment. Experimental data collected during the KAM11 experiment illustrates that for a two-user multiple-access system, multiuser separation can be achieved.
Annoyance due to railway vibration at different times of the day
Authors: Peris Eulalia , Woodcock James , Sica Gennaro , Moorhouse Andrew T. , Waddington David C.
Published: January 2012

The time of day when vibration occurs is considered as a factor influencing the human response to vibration. The aim of the present paper is to identify the times of day during which railway vibration causes the greatest annoyance, to measure the differences between annoyance responses for different time periods and to obtain estimates of the time of day penalties. This was achieved using data from case studies comprised of face-to-face interviews and internal vibration measurements (N = 755). Results indicate that vibration annoyance differs with time of day and that separate time of day weights can be applied when considering exposure–response relationships from railway vibration in residential environments.
Mixed Messages on Prices and Food Security
Authors: Swinnen Johan , Squicciarini Pasquamaria
Published: January 2012

We need a more nuanced debate on how prices and policies affect food security; neither high nor low prices are panaceas.
Comment on “Dynamics of Dpp Signaling and Proliferation Control”
Authors: Schwank Gerald , Yang Schu-Fee , Restrepo Simon , Basler Konrad
Published: January 2012

Wartlick
et al
. (Research Articles, 4 March 2011, p. 1154) reported that growth rates in the
Drosophila
wing disc correlate with increasing Dpp signaling levels, suggesting that the rate of Dpp increase determines the cell-cycle length. Contradicting their model, we found that cells in which the increase of Dpp signaling levels was genetically abrogated grew at rates comparable to those of wild-type cells.
Response to Comment on “Dynamics of Dpp Signaling and Proliferation Control”
Authors: Wartlick Ortrud , Mumcu Peer , Jülicher Frank , Gonzalez-Gaitan Marcos
Published: January 2012

Schwank
et al
. challenge the temporal growth model with an experiment in which Dpp signal transduction is abrogated. They claim that in this condition, cellular Dpp signaling levels do not increase over time but that cells do grow normally. We repeated this experiment and observed an increase of signaling over time. The results are consistent with a temporal model of growth control.
Crystal Structure of the Human Two–Pore Domain Potassium Channel K2P1
Authors: Miller Alexandria N. , Long Stephen B.
Published: January 2012

Potassium Permeation

Two–pore domain potassium (K2P) channels conduct K
+
ions across the plasma membrane of eukaryotic cells. They help to maintain the cellular resting potential and their modulation can tune cellular excitability (see the Perspective by

Poulsen and Nissen

).
Miller and Long
(p.
432
) describe a high-resolution crystal structure of the human K2P channel K2P1 (TWIK-1) and

Brohawn
et al.

(p.
436
) present a high-resolution structure of the lipid and mechanosensitive human channel TRAAK. In both structures an extracellular domain constricts the channel entrance so that K
+
ions reach the selectivity filter through side portals. Openings in the transmembrane region expose the central cavity to the lipid bilayer and a helix is kinked so that its C-terminal part lies in the cytosol-membrane interface. The structural features explain K2P conductance and gating and give insight into how the channels are regulated by diverse stimuli.
An Inquiry-Based Curriculum for Nonmajors
Authors: Jackson David P. , Laws Priscilla W. , Franklin Scott V.
Published: January 2012

Light, Sight, and Rainbows, the IBI prize-winning module, provides questions for exploring simple atmospheric phenomena.
Another Remembered Present
Authors: Meyer Kaspar
Published: January 2012

Could conscious perception reflect a memory process?
Global Correlations in Tropical Tree Species Richness and Abundance Reject Neutrality
Authors: Ricklefs Robert E. , Renner Susanne S.
Published: January 2012

Forest Diversification

The relative role of neutral and deterministic processes in generating species richness in ecological communities (particularly tropical trees) has dominated recent discussions about patterns of diversity and abundance of species.
Ricklefs and Renner
(p.
464
) present a test of random diversification and population change by comparing the numbers of individuals and species in plant families between forest plots on different continents that have diversified independently for millions of years. Stochastic theory, based on random events, predicts that there should be no correlation between the regions; however, the data reveal strong, statistically significant correlations. Thus, patterns of diversity appear to be dominated by deterministic processes.
A Long-Lived Lunar Core Dynamo
Authors: Shea Erin K. , Weiss Benjamin P. , Cassata William S. , Shuster David L. , Tikoo Sonia M. , Gattacceca Jérôme , Grove Timothy L. , Fuller Michael D.
Published: January 2012

Magnetic Moon

It has long been suspected that the Moon once had a core-dynamo magnetic field.

Shea
et al.

(p.
453
) describe a lunar basalt brought back by Apollo 11 that records evidence for a strong dynamo on the Moon 3.7 billion years ago. This study, together with a previous study of different lunar rock, implies that a lunar core dynamo existed between 4.2 and 3.7 billion years ago, which extends the known lifetime of the lunar dynamo by 500 million years.
Facilitated Cross-Species Transmission of Prions in Extraneural Tissue
Authors: Béringue Vincent , Herzog Laëtitia , Jaumain Emilie , Reine Fabienne , Sibille Pierre , Le Dur Annick , Vilotte Jean-Luc , Laude Hubert
Published: January 2012

Prion Problem

Prion disease, like “mad cow disease,” has shown a frightening ability to cross the species transmission barrier, but, mercifully, with low efficiency. However, the role of different tissues in prion cross-species transmission is unclear.

Béringue
et al.

(p.
472
; see the cover; see the Perspective by

Collinge

) compared the ability of brain and lymphoid tissues from “ovinized” (sheeplike) and “humanized” transgenic mouse models to replicate prion transmission across a robust transmission barrier. Lymphoid tissue of these mice was consistently more permissive than brain tissue to prions such as those causing chronic wasting disease and bovine spongiform encephalopathy. Because previous measures of the transmission barrier have focused on the brain, this heightened susceptibility of lymphoid tissues could strongly impact estimates of the number of silent carriers of prion disease.
A Clearer View from Fuzzy Images
Authors: Herberstein Marie E. , Kemp Darrel J.
Published: January 2012

Jumping spiders use defocus as a gauge of depth perception to locate prey.
Creating New Types of Carbon-Based Membranes
Authors: Paul Donald R.
Published: January 2012

Graphene oxide membranes can show unusually high water permeability, and diamond-like carbon membranes exhibited ultrafast permeation of organic solvents.
Antigen Feast or Famine
Authors: Dustin Michael L. , Meyer-Hermann Michael
Published: January 2012

The asymmetric distribution of antigen during B cell division affects the fate of B cells and their function.
Teaching Real Science
Authors: Alberts Bruce
Published: January 2012

In this issue of
Science
, we are publishing the first of 15 winning entries for the 2011
Science
Prize for Inquiry-Based Instruction (p. 418), a laboratory module entitled Light, Sight, and Rainbows. Created for introductory college science courses, each module can be readily used in many different settings and schools. The winning modules were selected by a jury of more than 70 scientists and science teachers, and the subjects include physics, math, chemistry, geology, molecular biology, plant science, and evolution. Throughout 2012, each will be published as a two-page printed synopsis supplemented by online material that contains the details needed to teach it.
Ron Fouchier: In the Eye of the Storm
Authors: Enserink Martin
Published: January 2012

Science
talked to Ron Fouchier of Erasmus MC in Rotterdam, the Netherlands, who carried out one of the two controversial H5N1 avian influenza studies that triggered the international debate.
Worldwide Telescope Aims to Look Into Milky Way Galaxy's Black Heart
Authors: Clery Daniel
Published: January 2012

Last week, astronomers gathered to work out a plan to combine data from radio telescopes worldwide and create, in effect, a dish the size of Earth that will be able to peer into our galaxy's heart.
DOE Funding Crunch Threatens Future of Only U.S. Collider Still Running
Authors: Cho Adrian
Published: January 2012

A $500 million upgrade planned for early next decade would enable the Relativistic Heavy Ion Collider to answer a key puzzle about the proton itself—if RHIC doesn't fall victim to budget cuts.
Modernizing an Academic Monastery
Authors: Miller Greg
Published: January 2012

The venerable Center for Advanced Study in the Behavioral Sciences has been trying to reinvent itself by applying behavioral science to 21st century problems.
Biochemical Characterization and Differential Expression of a 16.5-Kilodalton Tegument-Associated Antigen from the Liver Fluke Fasciola hepatica
Authors: Gaudier José F. , Cabán-Hernández Kimberly , Osuna Antonio , Espino Ana M.
Published: January 2012

A cDNA encoding a 16.5-kDa protein termed FhTP16.5 was identified by immunoscreening of a cDNA library fromFasciola hepaticaadult flukes using pooled sera from rabbits infected withF. hepaticafor 4 weeks. Quantitative reverse transcriptase PCR (qPCR) analysis revealed that FhTP16.5 is not expressed in unembryonated eggs. It is poorly expressed in miracidia and highly expressed at the juvenile and adult stages; however, significant differences were found between the expression levels of FhTP16.5 in juveniles versus adult flukes. Recombinant FhTP16.5 was expressed at high levels inEscherichia coli, purified by affinity chromatography, and used to raise anti-FhTP16.5 polyclonal antibodies in rabbits. Immunoblot analysis using the anti-FhTP16.5 IgG antibody identified FhTP16.5 in crude and tegumental extracts and in excretory-secretory products ofF. hepatica. The protein was not detected in crude extracts ofSchistosoma mansoniorSchistosomajaponicum. Antibodies to FhTP16.5 were detected in the sera of rabbits at 3 to 12 weeks ofF. hepaticainfection as well as in the sera of humans with chronic fascioliasis; these findings suggest that FhTP16.5 could be a good antigen for serodiagnosis of fascioliasis. Immunohistochemistry demonstrated that FhTP16.5 localizes to the surface of the tegument of various developmental stages and in parenchymal tissues of the adult fluke. Such specific localization makes FhTP16.5 an attractive target for immunoprophylaxis or chemotherapy.
Evaluation of a High-Throughput Diagnostic System for Detection of HIV-1 in Dried Blood Spot Samples from Infants in Mozambique
Authors: Jani Ilesh V. , Sabatier Jennifer , Vubil Adolfo , Subbarao Shambavi , Bila Dulce , de Sousa Amina , Mabunda Nédio , Garcia Albert , Skaggs Beth , Ellenberger Dennis , Ramos Artur
Published: January 2012

We performed a comparative analysis between Roche Amplicor HIV-1 DNA test and CAPTAQ assay for the detection of HIV in 830 dried blood spot (DBS) pediatric samples collected in Mozambique. Our results demonstrated no statistical difference between these assays. The CAPTAQ assay approached nearly 100% repeatability/accuracy. The increased throughput of testing with minimal operator interference in performing the CAPTAQ assay clearly demonstrated that this method is an improvement over the Roche Amplicor HIV-1 DNA test, version 1.5.
Development of a Human Herpesvirus 6 Species-Specific Immunoblotting Assay
Authors: Higashimoto Yuki , Ohta Akane , Nishiyama Yukihiro , Ihira Masaru , Sugata Ken , Asano Yoshizo , Peterson Daniel L. , Ablashi Dharam V. , Lusso Paolo , Yoshikawa Tetsushi
Published: January 2012

In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. The expression of these proteins was confirmed by using anti-His tag and 101K-specific monoclonal antibodies. HHV-6 species-specific antibodies were detected by immunoblotting in patient sera. Eighty-seven serum samples obtained from various subjects were utilized to determine the reliability of the method for clinical use. Ten of twelve exanthem subitum convalescent-phase sera reacted exclusively with 101K, whereas none of twelve acute-phase sera reacted with either protein. Two of three sera collected from HHV-6A-infected patients reacted with p100 and 101K. Although all five acute and convalescent-phase sera obtained from transplant recipients reacted exclusively with 101K, two of six convalescent-phase sera obtained from patients with drug-induced hypersensitivity syndrome reacted with both p100 and 101K. Of 38 sera obtained from healthy adults, 31 were positive for 101K antibody, while 4 reacted with both proteins. However, PCR analysis of peripheral blood mononuclear cells and saliva from these subjects did not detect HHV-6A DNA. In conclusion, this novel serological assay based on immunoblot analysis using recombinant HHV-6A p100 and HHV-6B 101K allowed us to discriminate between HHV-6A- and HHV-6B-specific antibodies.
Post-Kala-Azar Dermal Leishmaniasis in a Patient Treated with Injectable Paromomycin for Visceral Leishmaniasis in India
Authors: Pandey Krishna , Das V. N. R. , Singh Dharmendra , Das Sushmita , Lal C. S. , Verma N. , Bimal S. , Topno R. K. , Siddiqui N. A. , Verma R. B. , Sinha P. K. , Das Pradeep
Published: January 2012

Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation that usually develops after treatment of visceral leishmaniasis (VL), a major public health problem in India. The diagnosis and management of PKDL is complex. This is the first case report from India in which PKDL occurred after paromomycin treatment for VL in an Indian patient.
Scalp Abscess Due to Streptomyces cacaoi subsp.
cacaoi
, First Report in a Human Infection
Authors: Pellegrini Gerald J. , Graziano James C. , Ragunathan Latha , Bhat Malini A. , Hemashettar Basavaraj M. , Brown June M.
Published: January 2012

Streptomyces cacaoi
subsp.
cacaoi
, a Gram-positive, branching filamentous bacteria, was isolated from a scalp infection in a patient from Pondicherry, India. Phenotypic tests identified the isolate as a
Streptomyces
species, but 16S rRNA sequence analysis provided the species identification required for tracking of this emerging pathogen.
Role of Conserved Cysteine Residues in Hepatitis C Virus Glycoprotein E2 Folding and Function
Authors: McCaffrey Kathleen , Boo Irene , Tewierek Kevin , Edmunds Mark L. , Poumbourios Pantelis , Drummer Heidi E.
Published: January 2012

Hepatitis C virus glycoprotein E2 contains 18 conserved cysteines predicted to form nine disulfide pairs. In this study, a comprehensive cysteine-alanine mutagenesis scan of all 18 cysteine residues was performed in E1E2-pseudotyped retroviruses (HCVpp) and recombinant E2 receptor-binding domain (E2 residues 384 to 661 [E2
661
]). All 18 cysteine residues were absolutely required for HCVpp entry competence. The phenotypes of individual cysteines and pairwise mutation of disulfides were largely the same for retrovirion-incorporated E2 and E2
661
, suggesting their disulfide arrangements are similar. However, the contributions of each cysteine residue and the nine disulfides to E2 structure and function varied. Individual Cys-to-Ala mutations revealed discordant effects, where removal of one Cys within a pair had minimal effect on H53 recognition and CD81 binding (C486 and C569) while mutation of its partner abolished these functions (C494 and C564). Removal of disulfides at C581-C585 and C452-C459 significantly reduced the amount of E1 coprecipitated with E2, while all other disulfides were absolutely required for E1E2 heterodimerization. Remarkably, E2
661
tolerates the presence of four free cysteines, as simultaneous mutation of C452A, C486A, C569A, C581A, C585A, C597A, and C652A (M+C597A) retained wild-type CD81 binding. Thus, only one disulfide from each of the three predicted domains, C429-C552 (DI), C503-C508 (DII), and C607-C644 (DIII), is essential for the assembly of the E2
661
CD81-binding site. Furthermore, the yield of total monomeric E2 increased to 70% in M+C597A. These studies reveal the contribution of each cysteine residue and the nine disulfide pairs to E2 structure and function.
Deletions in the Neuraminidase Stalk Region of H2N2 and H9N2 Avian Influenza Virus Subtypes Do Not Affect Postinfluenza Secondary Bacterial Pneumonia
Authors: Chockalingam Ashok K. , Hickman Danielle , Pena Lindomar , Ye Jianqiang , Ferrero Andrea , Echenique Jose R. , Chen Hongjun , Sutton Troy , Perez Daniel R.
Published: January 2012

We investigated the synergism between influenza virus and
Streptococcus pneumoniae
, particularly the role of deletions in the stalk region of the neuraminidase (NA) of H2N2 and H9N2 avian influenza viruses. Deletions in the NA stalk (ΔNA) had no effect on NA activity or on the adherence of
S. pneumoniae
to virus-infected human alveolar epithelial (A549) and mouse lung adenoma (LA-4) cells, although it delayed virus elution from turkey red blood cells. Sequential
S. pneumoniae
infection of mice previously inoculated with isogenic recombinant H2N2 and H9N2 influenza viruses displayed severe pneumonia, elevated levels of intrapulmonary proinflammatory responses, and death. No differences between the WT and ΔNA mutant viruses were detected with respect to effects on postinfluenza pneumococcal pneumonia as measured by bacterial growth, lung inflammation, morbidity, mortality, and cytokine/chemokine concentrations. Differences were observed, however, in influenza virus-infected mice that were treated with oseltamivir prior to a challenge with
S. pneumoniae
. Under these circumstances, mice infected with ΔNA viruses were associated with a better prognosis following a secondary bacterial challenge. These data suggest that the H2N2 and H9N2 subtypes of avian influenza A viruses can contribute to secondary bacterial pneumonia and deletions in the NA stalk may modulate its outcome in the context of antiviral therapy.
Sangassou Virus, the First Hantavirus Isolate from Africa, Displays Genetic and Functional Properties Distinct from Those of Other Murinae-Associated Hantaviruses
Authors: Klempa Boris , Witkowski Peter T. , Popugaeva Elena , Auste Brita , Koivogui Lamine , Fichet-Calvet Elisabeth , Strecker Thomas , ter Meulen Jan , Krüger Detlev H.
Published: January 2012

We have discovered the first indigenous African hantavirus, Sangassou virus (SANGV). The virus was isolated from an African wood mouse (
Hylomyscus simus
), trapped in a forest habitat in Guinea, West Africa. Here, we report on the characterization of the genetic and functional properties of the virus. The complete genome of SANGV was determined and showed typical hantavirus organization. The small (S), medium (M), and large (L) genome segments containing genes encoding nucleocapsid protein, two envelope glycoproteins, and viral polymerase were found to be 1,746, 3,650, and 6,531 nucleotides long, respectively. The exact 5′ and 3′ termini for all three segments of the SANGV genome were determined and were predicted to form the panhandle structures typical of bunyaviruses. Phylogenetic analyses of all three segment sequences confirmed SANGV as a
Murinae
-associated hantavirus most closely related to the European Dobrava-Belgrade virus. We showed, however, that SANGV uses β
1
integrin rather than β
3
integrin and decay-accelerating factor (DAF)/CD55 as an entry receptor. In addition, we demonstrated a strong induction of type III lambda interferon (IFN-λ) expression in type I IFN-deficient Vero E6 cells by SANGV. These properties are unique within
Murinae
-associated hantaviruses and make the virus useful in comparative studies focusing on hantavirus pathogenesis.
Adenosine Deaminase Acting on RNA 1 (ADAR1) Suppresses the Induction of Interferon by Measles Virus
Authors: Li Zhiqun , Okonski Kristina M. , Samuel Charles E.
Published: January 2012

ADAR1, the interferon (IFN)-inducible adenosine deaminase acting on RNA, catalyzes the C-6 deamination of adenosine (A) to produce inosine (I) in RNA substrates with a double-stranded character. Because double-stranded RNA is a known inducer of IFN, we tested the role of ADAR1 in IFN induction following virus infection. HeLa cells made stably deficient in ADAR1 (ADAR1
kd
) were compared to vector control (CON
kd
) and protein kinase PKR-deficient (PKR
kd
) cells for IFN-β induction following infection with either parental (wild-type [WT]) recombinant Moraten vaccine strain measles virus (MV) or isogenic knockout mutants deficient for either V (V
ko
) or C (C
ko
) protein expression. We observed potent IFN-β transcript induction in ADAR1
kd
cells by all three viruses; in contrast, in ADAR1-sufficient CON
kd
cells, only the C
ko
mutant virus was an effective inducer and the IFN-β RNA induction was amplified by PKR. The enhanced IFN-β transcript-inducing capacity of the WT and V
ko
viruses seen in ADAR1-deficient cells correlated with the enhanced activation of PKR, IFN regulatory factor IRF3, and activator of transcription ATF2, reaching levels similar to those seen in C
ko
virus-infected cells. However, the level of IFN-β protein produced was not proportional to the level of IFN-β RNA but rather correlated inversely with the level of activated PKR. These results suggest that ADAR1 functions as an important suppressor of MV-mediated responses, including the activation of PKR and IRF3 and the induction of IFN-β RNA. Our findings further implicate a balanced interplay between PKR and ADAR1 in modulating IFN-β protein production following virus infection.
Correlation of Recombinant Integrase Activity and Functional Preintegration Complex Formation during Acute Infection by Replication-Defective Integrase Mutant Human Immunodeficiency Virus
Authors: Li Xiang , Koh Yasuhiro , Engelman Alan
Published: January 2012

Previous studies characterized two types of replication-defective human immunodeficiency virus type 1 (HIV-1) integrase mutants: class I, which are specifically blocked at the integration step, and class II, which harbor additional virion production and/or reverse transcription defects. Class I mutant enzymes supported little if any metal ion-dependent 3′-processing and DNA strand transfer activities
in vitro
, whereas class II enzymes displayed partial or full catalytic function in studies with simplified assay designs, suggesting that defective interaction(s) with heterologous integrase binding proteins might underlie the class II mutant viral phenotype. To address this hypothesis, class I and II mutant enzymes were interrogated under expanded sets of
in vitro
conditions. The majority failed to catalyze the concerted integration of two viral DNA ends into target DNA, highlighting defective integrase function as the root cause of most class II in addition to all class I mutant virus infection defects. One mutant protein, K264E, in contrast, could support the wild-type level of concerted integration activity. After accounting for its inherent reverse transcription defect, HIV-1
K264E
moreover formed preintegration complexes that supported the efficient integration of endogenous viral DNA
in vitro
and normal levels and sequences of 2-long terminal repeat-containing circle junctions during acute infection. K264E integrase furthermore efficiently interacted
in vitro
with two heterologous binding partners, LEDGF/p75 and reverse transcriptase. Our results underscore the physiological relevance of concerted integration assays for tests of integrase mutant function and suggest that the K264E mutation disrupts an interaction with an intranuclear integrase binding partner that is important for HIV-1 integration.
An Antibody Recognizing the Apical Domain of Human Transferrin Receptor 1 Efficiently Inhibits the Entry of All New World Hemorrhagic Fever Arenaviruses
Authors: Helguera Gustavo , Jemielity Stephanie , Abraham Jonathan , Cordo Sandra M. , Martinez M. Guadalupe , Rodríguez José A. , Bregni Carlos , Wang Jinyize J. , Farzan Michael , Penichet Manuel L. , Candurra Nélida A. , Choe Hyeryun
Published: January 2012

Five New World (NW) arenaviruses cause human hemorrhagic fevers. Four of these arenaviruses are known to enter cells by binding human transferrin receptor 1 (hTfR1). Here we show that the fifth arenavirus, Chapare virus, similarly uses hTfR1. We also identify an anti-hTfR1 antibody, ch128.1, which efficiently inhibits entry mediated by the glycoproteins of all five viruses, as well as replication of infectious Junín virus. Our data indicate that all NW hemorrhagic fever arenaviruses utilize a common hTfR1 apical-domain epitope and suggest that therapeutic agents targeting this epitope, including ch128.1 itself, can be broadly effective in treating South American hemorrhagic fevers.