bluuebunny/crossref_metadata_2025 huggingface dataset:
WEIGHT LOSS IN OBESE PATIENTS WITH CHRONIC KIDNEY DISEASE: WHO AND HOW?
Authors: Teta Daniel
Published: May 2010

Obesity has adverse consequences in the general population. In patients with chronic kidney disease (CKD), it is associated with increased inflammation, insulin resistance, hypertension and dyslipidaemia, which are important risk factors for CKD progression and death. In adults with CKD stages 1–4, weight loss should be encouraged, it reduces proteinuria and glomerular hyperfiltration, which are frequent in obese patients. Proposals for modifications of lifestyle, physical activity and calorie restriction are the first measures. Pharmacological treatments are generally unsafe in these patients, except orlistat, but that has modest efficacy. Bariatric surgery may be the only option in severe obesity, if all other measures fail. For obese patients on dialysis treatment, who are eligible for kidney transplantation, weight loss is mandatory to prevent obesity‐related surgical complications and improve patient and graft survival after transplantation. Interventions should place an emphasis on exercise to increase muscle mass, and calorie but not protein restriction. Bariatric surgery should be carried out by experienced surgeons due to the high risk of complications. For obese patients who are not considered transplant candidates the benefits of weight loss remain uncertain.
Isolation and genetic characterization of an improved benzene‐tolerant mutant of Pseudomonas putida S12
Authors: Volkers Rita J. M. , Ballerstedt Hendrik , De Winde Johannes H. , Ruijssenaars Harald J.
Published: May 2010

Pseudomonas putida S12.49, a mutant stain of P. putida S12 that tolerates up to 20 mM benzene, was obtained by evolutionary selection. The genetic basis for the strongly enhanced benzene tolerance was investigated by proteome and transcriptome analysis. Indications were found that the highly benzene‐tolerant phenotype is the resultant of multi‐level systemic changes. The solvent extrusion pump SrpABC was constitutively expressed in P. putida S12.49, which could be attributed to the disruption of the srpS regulator gene by the indigenous mutator element ISS12. The occurrence of this and two additional transposition events was in good agreement with the increased transcriptional activity of transposase‐encoding genes in strain S12.49. These observations suggested that transposition events are an important force driving the generation of the genetic diversity apparently required to obtain highly solvent‐tolerant phenotypes. In addition, various expression responses relating to energy generation indicated system changes that accommodated the energy demand associated with the high‐level expression of the proton‐driven solvent extrusion pump. The relatively modest effect of a respiratory chain uncoupler on benzene tolerance in P. putida S12.49 indicated the involvement of an alternative, non‐respiratory mechanism to maintain the proton gradient.
Plasmapheresis for neuroinflammatory disorders
Authors: Schröder Alexandra , Linker Ralf A. , Gold Ralf
Published: May 2010

Nowadays, therapeutic plasma exchange (PE) is the most common apheresis procedure. Plasma is separated from corpuscular blood constitutents and replaced with a substitution fluid. Thus, PE is a non‐specific treatment modality. Its therapeutic effect is based on the removal of circulating, pathogenic immune factors, including autoantibodies. To date, PE is well established for several immune mediated neurological disorders. Whilst the first experience was acquired in acute life‐threatening conditions, such as the treatment of Guillain–Barré syndrome or myasthenic crisis, therapeutic success was later achieved in other chronic autoimmune diseases; PE was applied successfully in chronic inflammatory demyelinating polyneuropathy, paraproteinaemic polyneuropathy, stiff‐person syndrome and might also be tried in autoimmune diseases of paraneoplastic origin. From a novel aspect, PE was also established as an escalation therapy for steroid unresponsive relapses of multiple sclerosis, and thus has gained even more widespread attention. Humoral disease mechanisms dominate even more in neuromyelitis optica, as a subtype of MS, and usually respond to PE. Adding to its increasing application in clinical practice, the procedure is usually well tolerated. Possible adverse reactions of PE arise from the large‐size vascular access site, the use of replacement fluids and the need for anticoagulation. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.0010.x, 2010)
Equine glaucomas
Authors: Ollivier F. , Monclin S.
Published: May 2010

The glaucomas are diseases that lead to the destruction of retinal ganglion cells and their axons via a number of mechanisms such as direct pressure damage, hypoxic and toxic injuries. The aim of this article is to present a review of this condition in horses in order to have a proactive attitude and to enable an early diagnosis to be made in order to determine the most adequate prophylactic (on predisposed individuals) and therapeutic treatment.
Development and Evaluation of a Prototype Solid Particle Receiver: On-Sun Testing and Model Validation
Authors: Siegel Nathan P. , Ho Clifford K. , Khalsa Siri S. , Kolb Gregory J.
Published: May 2010

A prototype direct absorption central receiver, called the solid particle receiver (SPR), was built and evaluated on-sun at power levels up to 2.5 MWth at Sandia National Laboratories in Albuquerque, NM. The SPR consists of a 6 m tall cavity through which spherical sintered bauxite particles are dropped and directly heated with concentrated solar energy. In principle, the particles can be efficiently heated to a temperature in excess of 900°C, well beyond the stability limit of existing nitrate salt formulations. The heated particles may then be stored in a way analogous to nitrate salt systems, enabling a dispatchable thermal input to power or fuel production cycles. The focus of this current effort was to provide an experimental basis for the validation of computational models that have been created to support improved designs and further development of the solid particle receiver. In this paper, we present information on the design and construction of the solid particle receiver and discuss the development of a computational fluid dynamics model of the prototype. We also present experimental data and model comparisons for on-sun testing of the receiver over a range of input power levels from 1.58–2.51 MWth. Model validation is performed using a number of metrics including particle velocity, exit temperature, and receiver efficiency. In most cases, the difference between the model predictions and data is less than 10%.
Dye-Sensitized Solar Cells Consisting of 3D-Electrodes—A Review: Aiming at High Efficiency From the View Point of Light Harvesting and Charge Collection
Authors: Uzaki Kenshiro , Nishimura Terumi , Usagawa Jun , Hayase Shuzi , Kono Mitsuru , Yamaguchi Yoshihiro
Published: May 2010

Directions to high efficiency dye-sensitized solar cells (DSCs) are reviewed in terms of light harvesting and charge collection. Three dimensional DSCs characterized by a double dye layer electrode, a floating electrode, and a fiber type electrode are proposed. The potentiality of each structure was discussed by using each model cell. Transparent conductive layerless electrodes were the key structures in these cells. Fabrication processes and fundamental performances are reported. Finally, it is concluded that dyes having high photoconversion efficiency in the near IR and IR regions are essential for realizing these tandem and hybrid cells.
Heliostat Shape and Orientation by Edge Detection
Authors: Röger Marc , Prahl Christoph , Ulmer Steffen
Published: May 2010

The heliostats of central receiver solar power plants reach dimensions up to 150 m2 with focal lengths up to 1000 m. Their optical properties and tracking accuracy have great influence on the power plant efficiency and need to be monitored both at plant start up and during operation. Up to now, there are few efficient and fast measurement techniques that allow the heliostat properties to be measured. Flux density measurements and close-range photogrammetry are possible approaches, yet they do not fulfill the requirement to be accurate, inexpensive, and fast at the same time. In this paper, we present a noncontact measurement principle, which uses edge detection to extract the heliostat and facet vertices. This information is used to calculate the surface normals. Furthermore, the corners can replace retroreflective targets generally used in close-range photogrammetry, thus, enabling a fast and completely automatic evaluation of the three-dimensional heliostat structure. The pictures are provided by a digital camera, which is mounted on a pan tilt head on top of the central receiver tower, offering visibility to all heliostats and allowing the automated qualification of whole heliostat fields in a short period of time. It is shown that measurement uncertainties in heliostat orientation for the investigated heliostat are below 4 mrad in 80% of the relevant heliostat positions. Heliostat orientation is available within three minutes. Photogrammetric measurements based on edge detection at a 40 m2 CESA-1 heliostat at the Plataforma Solar de Almerìa exhibit an accuracy of 1.6 mrad for a single-facet normal vector with the results being available within 30 min. The reduced measurement time allows the economic characterization of entire heliostat fields. The lower accuracy compared with manual photogrammetry with retroreflective targets is still sufficient to detect facet misalignments in existing heliostat fields.
Latent Heat Storage Systems for Solar Thermal Power Plants and Process Heat Applications
Authors: Steinmann Wolf-Dieter , Laing Doerte , Tamme Rainer
Published: May 2010

Solar thermal systems using absorber evaporating steam directly require isothermal energy storage. The application of latent heat storage systems is an option to fulfill this demand. This concept has been demonstrated mainly for low temperature heating and refrigeration applications, the experience for the power level and temperature range characteristic of solar process heat and solar thermal power plants is limited. Cost effective implementation of the latent heat storage concept demands low cost phase change materials (PCMs). These PCMs usually show low thermal conductivity limiting the power density during the charging/discharging process. This paper describes various approaches, which have been investigated to overcome these limitations. Based on fundamental PCM-research and laboratory-scale experiments, the sandwich concept has been identified to show the highest potential. The sandwich concept has been demonstrated successfully for three different storage units ranging from 2 kW to 100 kW at melting temperatures of 145°C and 225°C.
Experimental and Model Based Performance Analysis of a Linear Parabolic Trough Solar Collector in a High Temperature Solar Cooling and Heating System
Authors: Qu Ming , Yin Hongxi , Archer David H.
Published: May 2010

An innovative solar cooling and heating system has been designed, installed, tested, and modeled at Carnegie Mellon University to assess the technical and economic feasibility of high temperature solar cooling and heating system. This system primarily consists of parabolic trough solar collectors (PTSC) and a double effect absorption chiller. A comprehensive model for the tubular receiver of the PTSC has been developed to improve the PTSC design and overall system performance. The model has been verified by the experimental data from the tests on the PTSC in this system. The experimental data and theoretical analysis demonstrated that the properties of the glass envelope of PTSC significantly impacted the PTSC’s performance. The model calculations indicated that the vacuum in the annular space between the glass tube and absorber pipe of the PTSC does not markedly improve its efficiency. In addition, the system performance of the high temperature solar cooling and heating system has been presented and evaluated by using experimental data. Based on these model calculations, the performance of the PTSC installed has been projected and measures to improve the PTSC design have been recommended.
Cooperativity in Ion Hydration
Authors: Tielrooij K. J. , Garcia-Araez N. , Bonn M. , Bakker H. J.
Published: May 2010

Wet Twists and Turns

When salts dissolve in water, their constituent positively and negatively charged ions are pulled apart and surrounded by shells of H
2
O molecules (see the Perspective by

Skinner

).

Ji
et al.

(p.
1003
) looked closely at the motion in these shells, using a type of vibrational spectroscopy sensitive to both the orientation and to the neighbors of the targeted molecules. In agreement with recent theoretical predictions, the individual water molecules shifted orientation between an anion and the surrounding liquid in sudden discrete steps, rather than by making smooth incremental rotations.

Tielrooij
et al.

(p.
1006
) compared the relative impacts of cations and anions on the rigidity of the wider water network, using spectroscopic techniques sensitive to the role of each ion. Certain cation/anion combinations, such as magnesium sulfate, appeared to act together to restrict water motion beyond the boundaries of individual shells.
A Catalog of Reference Genomes from the Human Microbiome
Authors:   The Human Microbiome Jumpstart Reference Strains Consortium, Nelson Karen E. , Weinstock George M. , Highlander Sarah K. , Worley Kim C. , Creasy Heather Huot , Wortman Jennifer Russo , Rusch Douglas B. , Mitreva Makedonka , Sodergren Erica , Chinwalla Asif T. , Feldgarden Michael , Gevers Dirk , Haas Brian J. , Madupu Ramana , Ward Doyle V. , Birren Bruce W. , Gibbs Richard A. , Methe Barbara , Petrosino Joseph F. , Strausberg Robert L. , Sutton Granger G. , White Owen R. , Wilson Richard K. , Durkin Scott , Giglio Michelle Gwinn , Gujja Sharvari , Howarth Clint , Kodira Chinnappa D. , Kyrpides Nikos , Mehta Teena , Muzny Donna M. , Pearson Matthew , Pepin Kymberlie , Pati Amrita , Qin Xiang , Yandava Chandri , Zeng Qiandong , Zhang Lan , Berlin Aaron M. , Chen Lei , Hepburn Theresa A. , Johnson Justin , McCorrison Jamison , Miller Jason , Minx Pat , Nusbaum Chad , Russ Carsten , Sykes Sean M. , Tomlinson Chad M. , Young Sarah , Warren Wesley C. , Badger Jonathan , Crabtree Jonathan , Markowitz Victor M. , Orvis Joshua , Cree Andrew , Ferriera Steve , Fulton Lucinda L. , Fulton Robert S. , Gillis Marcus , Hemphill Lisa D. , Joshi Vandita , Kovar Christie , Torralba Manolito , Wetterstrand Kris A. , Abouellleil Amr , Wollam Aye M. , Buhay Christian J. , Ding Yan , Dugan Shannon , FitzGerald Michael G. , Holder Mike , Hostetler Jessica , Clifton Sandra W. , Allen-Vercoe Emma , Earl Ashlee M. , Farmer Candace N. , Liolios Konstantinos , Surette Michael G. , Xu Qiang , Pohl Craig , Wilczek-Boney Katarzyna , Zhu Dianhui
Published: May 2010

News from the Inner Tube of Life

A major initiative by the U.S. National Institutes of Health to sequence 900 genomes of microorganisms that live on the surfaces and orifices of the human body has established standardized protocols and methods for such large-scale reference sequencing. By combining previously accumulated data with new data,

Nelson
et al.

(p.
994
) present an initial analysis of 178 bacterial genomes. The sampling so far barely scratches the surface of the microbial diversity found on humans, but the work provides an important baseline for future analyses.
Observation of Plasmarons in Quasi-Freestanding Doped Graphene
Authors: Bostwick Aaron , Speck Florian , Seyller Thomas , Horn Karsten , Polini Marco , Asgari Reza , MacDonald Allan H. , Rotenberg Eli
Published: May 2010

More Crossings for Graphene

Graphene, which consists of single sheets of graphite, has a number of distinctive electronic properties, including a conical structure that leads to a “Dirac point” where the valence and conduction band intersect at a zero-energy point.

Bostwick
et al.

(p.
999
) used angle-resolved photoemission spectroscopy to study graphene that was doped with alkali atoms and suspended from its substrate. They observed features associated with plasmarons, which arise from the interaction of the charge carriers with plasmons, the density oscillations of the electron gas. The Dirac crossing now becomes three crossings: one that involves charge bands, one involving plasmarons, and one involving the interaction between the two.
Large Angular Jump Mechanism Observed for Hydrogen Bond Exchange in Aqueous Perchlorate Solution
Authors: Ji Minbiao , Odelius Michael , Gaffney K. J.
Published: May 2010

Wet Twists and Turns

When salts dissolve in water, their constituent positively and negatively charged ions are pulled apart and surrounded by shells of H
2
O molecules (see the Perspective by

Skinner

).

Ji
et al.

(p.
1003
) looked closely at the motion in these shells, using a type of vibrational spectroscopy sensitive to both the orientation and to the neighbors of the targeted molecules. In agreement with recent theoretical predictions, the individual water molecules shifted orientation between an anion and the surrounding liquid in sudden discrete steps, rather than by making smooth incremental rotations.

Tielrooij
et al.

(p.
1006
) compared the relative impacts of cations and anions on the rigidity of the wider water network, using spectroscopic techniques sensitive to the role of each ion. Certain cation/anion combinations, such as magnesium sulfate, appeared to act together to restrict water motion beyond the boundaries of individual shells.
Selfish Games

The Calculus of Selfishness
by Karl Sigmund

Princeton University Press, Princeton, NJ, 2010. 184 pp. $35, £24.95. ISBN 9780691142753. Theoretical and Computational Biology.
Authors: Krakauer David
Published: May 2010

Sigmund offers a fairly rigorous introduction to game-theory approaches to "interactions among individuals guided by self-interest and caught in social traps."
Following the Motions of Water Molecules in Aqueous Solutions
Authors: Skinner James L.
Published: May 2010

Ultrafast spectroscopy is revealing details of the rotational dynamics of water molecules in salt solutions.
The Enigmatic Inner Core
Authors: Buffett Bruce A.
Published: May 2010

Observations and models are beginning to explain the bewildering properties of Earth's solid inner core.
House Blocks Bill to Boost Research Spending
Authors: Mervis Jeffrey
Published: May 2010

The U.S. House of Representatives last week rejected legislation aimed at boosting research and education spending at three federal agencies due to concerns about the trillion-dollar federal deficit and the National Science Foundation's handling of employees who trafficked in electronic pornography at work.
TREM2- and DAP12-Dependent Activation of PI3K Requires DAP10 and Is Inhibited by SHIP1
Authors: Peng Qisheng , Malhotra Shikha , Torchia James A. , Kerr William G. , Coggeshall K. Mark , Humphrey Mary Beth
Published: May 2010

The inositol phosphatase SHIP1 binds to a receptor-adaptor complex on osteoclasts to prevent recruitment of PI3K and inhibit receptor signaling.
c-mip Impairs Podocyte Proximal Signaling and Induces Heavy Proteinuria
Authors: Zhang Shao-yu , Kamal Maud , Dahan Karine , Pawlak André , Ory Virginie , Desvaux Dominique , Audard Vincent , Candelier Marina , BenMohamed Fatima , Matignon Marie , Christov Christo , Decrouy Xavier , Bernard Veronique , Mangiapan Gilles , Lang Philippe , Guellaën Georges , Ronco Pierre , Sahali Djillali
Published: May 2010

Overexpression of the protein c-mip in mice produces phenotypes similar to various idiopathic kidney disorders.
Two Novel Antibiotic Resistance Genes,
tet
(44) and
ant(6)-Ib
, Are Located within a Transferable Pathogenicity Island in
Campylobacter fetus
subsp.
fetus
Authors: Abril Carlos , Brodard Isabelle , Perreten Vincent
Published: May 2010

New tetracycline and streptomycin resistance genes,
tet
(44) and
ant(6)-Ib
, were identified in
Campylobacter fetus
subsp.
fetus
within a transferable pathogenicity island that is typically unique to
Campylobacter fetus
subsp.
venerealis
. The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class of proteins that confers resistance to tetracycline and minocycline by ribosomal protection. The 286-amino-acid streptomycin resistance determinant, ANT(6)-Ib, belongs to a family of aminoglycoside nucleotidyltransferases. The resistance phenotypes were demonstrated by gene inactivation and expression.
Engineering of
Lactobacillus jensenii
To Secrete RANTES and a CCR5 Antagonist Analogue as Live HIV-1 Blockers
Authors: Vangelista Luca , Secchi Massimiliano , Liu Xiaowen , Bachi Angela , Jia Letong , Xu Qiang , Lusso Paolo
Published: May 2010

The development of effective microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of AIDS epidemics worldwide. A promising strategy is the use of bacteria belonging to the vaginal microbiota as live microbicides for the topical production of HIV-1 inhibitors. We have engineered a human vaginal isolate of
Lactobacillus jensenii
to secrete the anti-HIV-1 chemokine RANTES, as well as C1C5 RANTES, a mutated analogue that acts as a CCR5 antagonist and therefore is devoid of proinflammatory activity. Full-length wild-type RANTES and C1C5 RANTES secreted by
L. jensenii
were purified to homogeneity and shown to adopt a correctly folded conformation. Both RANTES variants were shown to inhibit HIV-1 infection in CD4
+
T cells and macrophages, displaying strong activity against HIV-1 isolates of different genetic subtypes. This work provides proof of principle for the use of
L. jensenii
-produced C1C5 RANTES to block HIV-1 infection of CD4
+
T cells and macrophages, setting the basis for the development of a live anti-HIV-1 microbicide targeting CCR5 in an antagonistic manner.
Secondary Integrase Resistance Mutations Found in HIV-1 Minority Quasispecies in Integrase Therapy-Naive Patients Have Little or No Effect on Susceptibility to Integrase Inhibitors
Authors: Ceccherini-Silberstein Francesca , Van Baelen Kurt , Armenia Daniele , Trignetti Maria , Rondelez Evelien , Fabeni Lavinia , Scopelliti Fernanda , Pollicita Michela , Van Wesenbeeck Liesbeth , Van Eygen Veerle , Dori Luca , Sarmati Loredana , Aquaro Stefano , Palamara Guido , Andreoni Massimo , Stuyver Lieven J. , Perno Carlo Federico
Published: May 2010

The goal of this study was to explore the presence of integrase strand transfer inhibitor (InSTI) resistance mutations in HIV-1 quasispecies present in InSTI-naïve patients and to evaluate theirin vitroeffects on phenotypic susceptibility to InSTIs and their replication capacities. The RT-RNase H-IN region was PCR amplified from plasma viral RNA obtained from 49 HIV-1 subtype B-infected patients (21 drug naïve and 28 failing highly active antiretroviral therapy [HAART] not containing InSTIs) and recombined with an HXB2-based backbone with RT and IN deleted. Recombinant viruses were tested against raltegravir and elvitegravir and for replication capacity. Three-hundred forty-four recombinant viruses from 49 patients were successfully analyzed both phenotypically and genotypically. The majority of clones were not phenotypically resistant to InSTIs: 0/344 clones showed raltegravir resistance, and only 3 (0.87%) showed low-level elvitegravir resistance. No primary resistance mutations for raltegravir and elvitegravir were found as major or minor species. The majority of secondary mutations were also absent or rarely present. Secondary mutations, such as T97A and G140S, found rarely and only as minority quasispecies, were present in the elvitegravir-resistant clones. A novel mutation, E92G, although rarely found in minority quasispecies, showed elvitegravir resistance. Preexisting genotypic and phenotypic raltegravir resistance was extremely rare in InSTI-naïve patients and confined to only a restricted minority of secondary variants. Overall, these results, together with others based on population and ultradeep sequencing, suggest that at this point IN genotyping in all patients before raltegravir treatment may not be cost-effective and should not be recommended until evidence of transmitted drug resistance to InSTIs or the clinical relevance of IN minor variants/polymorphisms is determined.
Investigating the Induction of Vaccine-Induced Th17 and Regulatory T Cells in Healthy,Mycobacterium bovisBCG-Immunized Adults Vaccinated with a New Tuberculosis Vaccine, MVA85A
Authors: de Cassan Simone C. , Pathan Ansar A. , Sander Clare R. , Minassian Angela , Rowland Rosalind , Hill Adrian V. S. , McShane Helen , Fletcher Helen A.
Published: May 2010

Tuberculosis (TB) remains a threat to global health. While advances in diagnostics and treatment are crucial to the containment of the epidemic, it is likely that elimination of the disease can only be achieved through vaccination. Vaccine-induced protection fromMycobacterium tuberculosisis dependent, at least in part, on a robust Th1 response, yet little is known of the ability of TB vaccines to induce other T-cell subsets which may influence vaccine efficacy. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by Th17 cells which has been associated with both immune pathology and protection against infectious disease. Following vaccination with MVA85A, a viral vector vaccine aimed at enhancing immune responses toM. tuberculosis, antigen-specific IL-17A-producing T cells were induced in the peripheral blood of healthy volunteers. These T cells are detected later than gamma interferon (IFN-γ)-secreting T cells and are of a low magnitude. Preexisting immune responses to mycobacterial antigens were associated with higher CD4+CD25hiCD39+T-cell levels in the periphery and a reduced capacity to produce IL-17A following immunization. These data highlight the intricate balance of effector and regulatory immune responses induced by vaccination and that preexisting immunity to mycobacterial antigens may affect the composition of vaccine-induced T-cell subsets.
Immune Responses to Recombinant Pneumococcal PsaA Antigen Delivered by a Live Attenuated
Salmonella
Vaccine
Authors: Wang Shifeng , Li Yuhua , Shi Huoying , Scarpellini Giorgio , Torres-Escobar Ascencion , Roland Kenneth L. , Curtiss Roy
Published: May 2010

Streptococcus pneumoniae
is a leading cause of morbidity and mortality among children worldwide and particularly in developing countries. In this study, we evaluated PsaA, a conserved antigen important for
S. pneumoniae
adhesion to and invasion into nasopharynx epithelia, for its ability to induce protective immunity against
S. pneumoniae
challenge when delivered by recombinant attenuated
Salmonella
vaccine (RASVs) strains. RASVs were engineered to synthesize PsaA peptides of various lengths. Vaccination with an RASV synthesizing full-length PsaA induced high titers of anti-PsaA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes, nasal washes, and lung homogenates) sites. BALB/c (haplotype H2
d
) or C57BL/6 (haplotype H2
b
) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with
S. pneumoniae
strains compared to controls, although protection was not observed with all challenge strains. None of the vaccine constructs provided protection against intraperitoneal challenge with
S. pneumoniae
strain WU2 (serotype 3). Immunization with RASVs synthesizing truncated PsaA generated lower titers of IgA and IgG and did not provide significant protection. Our results showed that RASVs synthesizing full-length PsaA can provide protection against nasal colonization by some
S. pneumoniae
strains. PsaA may be a useful addition to a multivalent vaccine, providing protection against pneumonia, otitis media, and other diseases caused by
S. pneumoniae
.
Comparison of the Eragen Multi-Code Respiratory Virus Panel with Conventional Viral Testing and Real-Time Multiplex PCR Assays for Detection of Respiratory Viruses
Authors: Arens Max Q. , Buller Richard S. , Rankin Anne , Mason Sheila , Whetsell Amy , Agapov Eugene , Lee Wai-Ming , Storch Gregory A.
Published: May 2010

High-throughput multiplex assays for respiratory viruses are an important step forward in diagnostic virology. We compared one such assay, the PLx Multi-Code Respiratory Virus Panel (PLx-RVP), manufactured by Eragen Biosciences, Inc. (Madison, WI), with conventional virologic testing, consisting of fluorescent-antibody staining plus testing with the R-mix system and fibroblast tube cultures. The test set consisted of 410 archived respiratory specimens, mostly nasopharyngeal swabs, including 210 that had been positive by conventional testing for a balanced selection of common respiratory viruses. Specimens yielding discrepant results were evaluated using a panel of respiratory virus PCR assays developed, characterized, and validated with clinical specimens. PLx-RVP increased the total rate of detection of viruses by 35.8%, and there was a 25.7% increase in the rate of detection of positive specimens. Reference PCR assay results corroborated the PLx-RVP result for 54 (82%) of 66 discrepancies with conventional testing. Of the 12 specimens with discrepancies between PLx-RVp and the reference PCRs, 6 were positive for rhinovirus by PLx-RVP and the presence of rhinovirus was confirmed by nucleotide sequencing. The remaining six specimens included five in which the PLx-RVP failed to detect parainfluenza virus and one in which the detection of influenza A virus by PLx-RVP could not be confirmed by the reference PCR. Taking the results of the reference PCR assay results into account, the sensitivities of the PLx-RVP for individual viruses ranged from 94 to 100% and the specificities ranged from 99 to 100%. We conclude that PLx-RVP is a highly accurate system for the detection of respiratory viruses and significantly improves the rate of detection of these viruses compared to that by conventional virologic testing.
Development of Microsphere-Based Multiplex Branched DNA Assay for Detection and Differentiation of Avian Influenza Virus Strains
Authors: Cha Wonhee , Ma Yunqing , Saif Yehia Mo , Lee Chang-Won
Published: May 2010

We developed and evaluated a multiplex branched DNA assay for the detection and subtyping of avian influenza (AI) virus strains. The assay successfully detected all 94 AI virus strains of 15 different hemagglutinin (HA) subtypes tested while simultaneously differentiating 24 North American H5, 11 Eurasian H5, and 11 H7 strains. Our study demonstrates for the first time that a branched DNA method can detect targets that show a great amount of sequence variation.
Switching of Inferred Tropism Caused by HIV during Interruption of Antiretroviral Therapy
Authors: Sarmati L. , Parisi S. G. , Andreoni C. , Nicastri E. , Buonomini A. R. , Boldrin C. , Dori L. , Montano M. , Tommasi C. , Andreis S. , Vullo V. , Palù G. , Andreoni M.
Published: May 2010

After interruption of highly active antiretroviral therapy, 15 out of 53 patients with the X4 HIV strain had a significantly larger decrease in CD4
+
T cell count (
P
= 0.001) and shorter length of treatment interruption (
P
= 0.02) than patients with the R5 strain. At treatment resumption, HIV inferred tropism switched from the X4 strain to the R5 variant in 9 patients (60%). These patients had a prolonged length of treatment interruption compared to that of those who still carried the X4 strain.
Outbreak of Canine Norovirus Infection in Young Dogs
Authors: Ntafis Vasileios , Xylouri Eftychia , Radogna Arianna , Buonavoglia Canio , Martella Vito
Published: May 2010

An outbreak of norovirus (NoV) infection was identified in a kennel. Sequence analysis of a short fragment in the polymerase complex indicated the clonal origin of the strains, which were similar to the prototype canine NoV strain GIV.2/Bari/170/07-4/ITA (94.7% nucleotide identity). The findings demonstrate that canine NoV circulates in dogs in Greece and that it can spread easily across a group of animals.
The Putative Pocket Protein Binding Site of
Autographa californica
Nucleopolyhedrovirus BV/ODV-C42 Is Required for Virus-Induced Nuclear Actin Polymerization
Authors: Li Kun , Wang Yun , Bai Huimin , Wang Qian , Song Jianhua , Zhou Yuan , Wu Chunchen , Chen Xinwen
Published: May 2010

Nuclear filamentous actin (F-actin) is essential for nucleocapsid morphogenesis of lepidopteran nucleopolyhedroviruses. Previously, we had demonstrated that
Autographa californica
multiple nucleopolyhedrovirus (
Ac
MNPV) BV/ODV-C42 (C42) is involved in nuclear actin polymerization by recruiting P78/83, an
Ac
MNPV
orf9
-encoded N-WASP homology protein that is capable of activating an actin-related-protein 2/3 (Arp2/3) complex to initiate actin polymerization, to the nucleus. To further investigate the role of C42 in virus-induced actin polymerization, the recombinant bacmid vAc
p78/83nls-gfp
, with a
c42
knockout,
p78/83
tagged with a nuclear localization signal coding sequence, and
egfp
as a reporter gene under the control of the
Pp10
promoter, was constructed and transfected to Sf9 cells. In the nuclei of vAc
p78/83nls-gfp
-transfected cells, polymerized F-actin filaments were absent, whereas other actin polymerization elements (i.e., P78/83, G-actin, and Arp2/3 complex) were present. This
in vivo
evidence indicated that C42 actively participates in the nuclear actin polymerization process as a key element, besides its role in recruiting P78/83 to the nucleus. In order to collect
in vitro
evidence for the participation of C42 in actin polymerization, an anti-C42 antibody was used to neutralize the viral nucleocapsid, which is capable of initiating actin polymerization
in vitro
. Both the kinetics of pyrene-actin polymerization and F-actin-specific staining by phalloidin indicated that anti-C42 can significantly attenuate the efficiency of F-actin formation compared to that with control antibodies. Furthermore, we have identified the putative pocket protein binding sequence (PPBS) on C42 that is essential for C42 to exert its function in nuclear actin polymerization.
Differential Expression of the miR-200 Family MicroRNAs in Epithelial and B Cells and Regulation of Epstein-Barr Virus Reactivation by the miR-200 Family Member miR-429
Authors: Lin Zhen , Wang Xia , Fewell Claire , Cameron Jennifer , Yin Qinyan , Flemington Erik K.
Published: May 2010

The miR-200 microRNA family is important for maintaining the epithelial phenotype, partially through suppressing ZEB1 and ZEB2. Since ZEB1 inhibits Epstein-Barr virus (EBV) reactivation, we hypothesized that expression of miR-200 family members in epithelial cells may partly account for higher levels of EBV reactivation in this tissue (relative to nonplasma B cells). Here we show that, whereas miR-200 family members are expressed in epithelial cells, their expression is low in latently infected B cells. Furthermore, the miR-200 family member miR-429 shows elevated expression in plasma cell lines and is induced by B-cell-receptor activation in Akata cells. Lastly, expression of miR-429 can break latency.
Phosphatidylinositol 3-Kinase-, Actin-, and Microtubule-Dependent Transport of Semliki Forest Virus Replication Complexes from the Plasma Membrane to Modified Lysosomes
Authors: Spuul Pirjo , Balistreri Giuseppe , Kääriäinen Leevi , Ahola Tero
Published: May 2010

Like other positive-strand RNA viruses, alphaviruses replicate their genomes in association with modified intracellular membranes. Alphavirus replication sites consist of numerous bulb-shaped membrane invaginations (spherules), which contain the double-stranded replication intermediates. Time course studies with Semliki Forest virus (SFV)-infected cells were combined with live-cell imaging and electron microscopy to reveal that the replication complex spherules of SFV undergo an unprecedented large-scale movement between cellular compartments. The spherules first accumulated at the plasma membrane and were then internalized using an endocytic process that required a functional actin-myosin network, as shown by blebbistatin treatment. Wortmannin and other inhibitors indicated that the internalization of spherules also required the activity of phosphatidylinositol 3-kinase. The spherules therefore represent an unusual type of endocytic cargo. After endocytosis, spherule-containing vesicles were highly dynamic and had a neutral pH. These primary carriers fused with acidic endosomes and moved long distances on microtubules, in a manner prevented by nocodazole. The result of the large-scale migration was the formation of a very stable compartment, where the spherules were accumulated on the outer surfaces of unusually large and static acidic vacuoles localized in the pericentriolar region. Our work highlights both fundamental similarities and important differences in the processes that lead to the modified membrane compartments in cells infected by distinct groups of positive-sense RNA viruses.
Cross-Reactive Neutralizing Antibodies Directed against Pandemic H1N1 2009 Virus Are Protective in a Highly Sensitive DBA/2 Mouse Influenza Model
Authors: Boon Adrianus C. M. , deBeauchamp Jennifer , Krauss Scott , Rubrum Adam , Webb Ashley D. , Webster Robert G. , McElhaney Janet , Webby Richard J.
Published: May 2010

Our ability to rapidly respond to an emerging influenza pandemic is hampered somewhat by the lack of a susceptible small-animal model. To develop a more sensitive model, we pathotyped 18 low-pathogenic non-mouse-adapted influenza A viruses of human and avian origin in DBA/2 and C57BL/6 mice. The majority of the isolates (13/18) induced severe morbidity and mortality in DBA/2 mice upon intranasal challenge with 1 million infectious doses. Also, at a 100-fold-lower dose, more than 50% of the viruses induced severe weight loss, and mice succumbed to the infection. In contrast, only two virus strains were pathogenic for C57BL/6 mice upon high-dose inoculation. Therefore, DBA/2 mice are a suitable model to validate influenza A virus vaccines and antiviral therapies without the need for extensive viral adaptation. Correspondingly, we used the DBA/2 model to assess the level of protection afforded by preexisting pandemic H1N1 2009 virus (H1N1pdm) cross-reactive human antibodies detected by a hemagglutination inhibition assay. Passive transfer of these antibodies prior to infection protected mice from H1N1pdm-induced pathogenicity, demonstrating the effectiveness of these cross-reactive neutralizing antibodiesin vivo.
Upregulation of the Chemokine (C-C Motif) Ligand 2 via a Severe Acute Respiratory Syndrome Coronavirus Spike-ACE2 Signaling Pathway
Authors: Chen I-Yin , Chang Shin C. , Wu Hung-Yi , Yu Ting-Chun , Wei Wen-Chin , Lin Shiming , Chien Chung-Liang , Chang Ming-Fu
Published: May 2010

Severe acute respiratory syndrome coronavirus (SARS-CoV) was identified to be the causative agent of SARS with atypical pneumonia. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for SARS-CoV. It is not clear whether ACE2 conveys signals from the cell surface to the nucleus and regulates expression of cellular genes upon SARS-CoV infection. To understand the pathogenesis of SARS-CoV, human type II pneumocyte (A549) cells were incubated with the viral spike protein or with SARS-CoV virus-like particles containing the viral spike protein to examine cytokine modulation in lung cells. Results from oligonucleotide-based microarray, real-time PCR, and enzyme-linked immunosorbent assays indicated an upregulation of the fibrosis-associated chemokine (C-C motif) ligand 2 (CCL2) by the viral spike protein and the virus-like particles. The upregulation of CCL2 by SARS-CoV spike protein was mainly mediated by extracellular signal-regulated kinase 1 and 2 (ERK1/2) and AP-1 but not the IκBα-NF-κB signaling pathway. In addition, Ras and Raf upstream of the ERK1/2 signaling pathway were involved in the upregulation of CCL2. Furthermore, ACE2 receptor was activated by casein kinase II-mediated phosphorylation in cells pretreated with the virus-like particles containing spike protein. These results indicate that SARS-CoV spike protein triggers ACE2 signaling and activates fibrosis-associated CCL2 expression through the Ras-ERK-AP-1 pathway.
Electrochemical behaviour of 2,5-dihydroxyanisole on a mercury electrode in aqueous media
Authors: Sazou Dimitra , Poulios Ioannis
Published: May 2010

Electrochemical investigation of 2,5-dihydroxyanisole (2,5-DHA) has been carried out in aqueous solutions in pH range 2-11 on hanging mercury drop electrode (HMDE). The oxidation process in pH range 2-6 is a quasi-reversible electrode reaction which involves the transfer of two electrons and two protons. By use of semi-integration a dependence of the heterogeneous rate constant on the potential has been appreciated. Thus, the variation of peak current with pH changes can be explained. In more basic solutions the electrooxidation is complicated by subsequent chemical reactions as indicated from the calculated voltammetric and chronoamperometric parameters.
Effect of halides on the reaction of aluminium single crystal in aqueous sodium hydroxide
Authors: Šiška Jozef , Miadoková Milica , Vítková Mária
Published: May 2010

The effect of sodium halides on the reaction rate and potential of an aluminium single crystal in aqueous solution NaOH is studied. Fluoride, bromide and iodide ions exert an inhibiting effect, which is explained in terms of their specific adsorption on the solid surface, whereas chloride ions have a stimulating effect on the reaction rate, presumably due to the formation of complex surface intermedates.
New statistical parameters for description of solvent effect
Authors: Pytela Oldřich
Published: May 2010

A new three-parameter statistical scale has been suggested to describe the solvent effect. The parameters were obtained by applying the method of conjugated deviations (suggested earlier by the author) to a set of 378 data series describing the solvent effect in various chemical and physical processes. The first parameter PA describes the solvent acidity in a medium of a given polarity, the second parameter PB predominantly reflects the solvent polarity with a contribution of basicity, and the third parameter PP refers to the polarity with a contribution of polarizability. The correlation equation, though additive by its form, is de facto an additive-multiplicative relation. Deviations of the parameters indicate a great variability of the solvent effect due to specific manifestations in particular systems. The correlations using the definition set of processes were most successful in the case of the data obtained from kinetic measurements and electronic and infrared spectra. Less significant correlations were obtained for the data from NMR and EPR spectroscopies and measurements of equilibrium constants. Distinctly worse results were found for other processes. The comparison with four most significant empirical equations applied to the same data was unambiguously in favour of the scale suggested (except for the interpretation of EPR data.
Photochemical synthesis of 4-ethoxycarbonyl-5-hydroxypyrazoles
Authors: Spassova Maria K. , Zakharieva Rossitza D.
Published: May 2010

The photochemical decomposition of 4-ethoxycarbonyl-5-diazopyrazoles in tetrafluoroboric acid results in corresponding 4-ethoxycarbonyl-5-hydroxypyrazoles (V-VII). The irradiation of the diazocompound in dioxane, toluene or tetrahydrofurane proceeds with a reductive decomposition producing corresponding 4-ethoxycarbonylpyrazole (VIII) as the main photoproduct.
2-Amino-substituted derivatives of benzimidazoles from 2-isothiocyanato carboxylates
Authors: Floch Ľubomír , Uher Michal , Leško Ján
Published: May 2010

2-Isothiocyanato carboxylates react with o-phenylenediamine to give N,N'-substituted thioureas, which cyclize to yield 2-amino-substituted derivatives of imidazole. The structure of these compounds was corroborated by IR, UV, 1H, 13C NMR, and mass spectral methods.
Potential antidepressants: Synthesis of two 4-(aminoalkoxy)dibenzo[b,e]thiepin-11(6H)-ones
Authors: Červená Irena , Holubek Jiří , Svátek Emil , Metyš Jan , Valchář Martin , Protiva Miroslav
Published: May 2010

Heating of 4-methoxydibenzo[b,e]thiepin-11(6H)-one with pyridine hydrochloride to 225 to 235 °C effected demethylation and gave IV. Its sodium salt reacted with 3-dimethylaminopropyl chloride in ethanol and afforded the 4-(3-dimethylaminopropoxy) compound II. The isomeric ether III was prepared via the 4-(4-bromobutoxy) compound V. Hydrochloride of II (VÚFB-17 033) inhibited mildly the binding of [3H]desipramine in rat hypothalamus, had antireserpine activity in rats, mild anticonvulsant effect, and antihypoxic effect in the test of nitrogen anoxia in mice.
Potential antidepressants: 2-(6,11-Dihydrodibenzo[b,e]thiepin-11-yl)-4,5-dihydroimidazoles
Authors: Šindelář Karel , Metyšová Jiřina , Protiva Miroslav
Published: May 2010

Reactions of 2-substituted 11-chloro-6,11-dihydrodibenzo[b,e]thiepins with trimethylsilyl cyanide in dichloromethane in the presence of stannic chloride afforded nitriles IIb-IId in high yields. Heating of IIa-IId with 2-aminoethylammonium toluene-4-sulfonate to 200 °C gave the title compounds Ia-Id which were transformed to hydrogen maleates. Compound Ic (hydrogen maleate VÚFB-17 092) showed in several tests a clear thymoleptic (potential antidepressant) character.
Branched-chain derivatives of acyclic adenosine analogs: Alkyl and hydroxymethyl derivatives of S-adenosyl-L-homocysteinase inhibitors substituted at the 2- and 3-position of the side chain
Authors: Holý Antonín
Published: May 2010

Reaction of 1,3-dichloro-2-propanone (VII) with methylmagnesium chloride, followed by alkaline hydrolysis, afforded 2-methylpropane-1,2,3-triol (VIII) which on treatment with 2,2-dimethoxypropane and subsequent tosylation gave 4-(p-toluenesulfonyloxymethyl)-2,2,4-trimethyl-1,3-dioxolane (IXb). Compound IXb was condensed with sodium salt of adenine and the intermediate X was acid-hydrolysed to give 9-(RS)-(2,3-dihydroxy-2-methylpropyl)adenine (XI). Oxidation of XI with sodium periodate led to 9-(2-oxopropyl)adenine (XII). 9-(RS)-(2-Hydroxy-2-hydroxymethyloctyl)adenine (XVI) was obtained analogously from compound VII and hexylmagnesium bromide via triol XIV. Methyl 2-bromomethyl-2-propenoate (XVII) reacted with sodium salt of adenine and the resulting methyl 2-(adenin-9-ylmethyl)-2-propenoate (XVIII) was hydroxylated with sodium perchlorate and osmium tetroxide. The obtained methyl (RS)-2-(adenin-9-ylmethyl)-2,3-dihydroxypropanoate (XIX) was alkali-hydrolysed to give sodium salt of the acid XX. Reduction of ester XIX with sodium borohydride furnished 9-(RS)-(2,3-dihydroxy-2-hydroxymethylpropyl)adenine (XXI). 1-Nonen-3-ol (XXIII), obtained by reaction of propenal with hexylmagnesium bromide, was converted by hydroxylation with osmium tetroxide into nonane-1,2,3-triol (XXIVa) and further into its 1-O-p-toluenesulfonate XXIVb which reacted with 2,2-dimethoxypropane to give 2,2-dimethyl-4-hexyl-5-(p-toluenesulfonyloxymethyl)-1,3-dioxolane (XXV). Compound XXV reacted with adenine and the resulting intermediate XXVI was converted into 9-(RS)-(2,3-dihydroxynonyl)adenine (XXVII) by acid hydrolysis. 9-(3-Methyl-2-buten-1-yl)adenine (XXVIII), obtained by alkylation of sodium salt of adenine with 1-bromo-3-methyl-2-butene, was oxidized with potassium permanganate in an acid medium to give 9-(3-hydroxy-2-oxo-3-methylbutyl)adenine (XXIX). This compound was converted into 9-(RS)-(2,3-dihydroxy-3-methylbutyl)adenine (XXX) by reduction with sodium borohydride. 4-C-Hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose (XXXII) reacted with 2,2-dimethoxypropane under formation of 4-C-hydroxymethyl-1,2:3,5-di-O-isopropylidene derivative XXXIIIa whose p-toluenesulfonyl derivative XXXIIIb on treatment with adenine afforded 4-C-(adenin-9-yl)methyl-1,2:3,5-di-O-isopropylidene-α-D-xylofuranose (XXXIV). Acid hydrolysis of this compound, followed by oxidation in an alkaline medium, gave (2S,3R)-4-(adenin-9-yl)-3-hydroxymethyl-2,3-dihydroxybutanoic acid, isolated as its ethyl ester XXXVI.