bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonographic evaluation of thyroid morphology during different reproductive events in female Indo‐Pacific bottlenose dolphins, Tursiops aduncus
Authors: Kot Brian C. W. , Ying Michael T. C. , Brook Fiona M. , Kinoshita Reimi E. , Kane David , Chan Winson K.
Published: September 2011

Abstract

Thyroid morphology and function are likely affected by the cyclic hormonal environment during different reproductive events in females. The present study was undertaken to evaluate the variation of thyroid morphology at different reproductive events (anestrus, estrus, lactation, and pregnancy) in a captive group of Indo‐Pacific bottlenose dolphins (Tursiops aduncus) measured using sonography. Sonographic examinations of the thyroid gland and ovaries in nine sexually mature female subjects were performed weekly for 2.5 yr. A generalized linear mixed model was used to estimate the effects of the reproductive events for thyroid volume. Reproductive event was found to be a significant predictor for thyroid volume measurement and significant variation in thyroid volume was found between different reproductive events. A significantly larger thyroid volume in lactating females was observed when compared with estrous and anestrous females, possibly due to the high energy requirements and milk production during lactation. Taken together, thyroid volume variation during different reproductive events in female dolphins should be considered so as to obtain a diagnostically meaningful assessment when conducting routine examinations.
Phlorotannin Production and Lipid Oxidation as a Potential Protective Function Against High Photosynthetically Active and UV Radiation in Gametophytes of Alaria esculenta (Alariales, Phaeophyceae)
Authors: Steinhoff Franciska S. , Graeve Martin , Bartoszek Krzysztof , Bischof Kai , Wiencke Christian
Published: September 2011

Radiation damage can inter alia result in lipid peroxidation of macroalgal cell membranes. To prevent photo‐oxidation within the cells, photoprotective substances such as phlorotannins are synthesized. In the present study, changes in total fatty acids (FA), FA composition and intra/extracellular phlorotannin contents were determined by gas chromatography and the Folin‐Ciocalteu method to investigate the photoprotective potential of phlorotannins to prevent lipid peroxidation. Alaria esculenta juveniles (Phaeophyceae) were exposed over 20 days to high/low photosynthetically active radiation (PAR) in combination with UV radiation (UVR) in the treatments: PAB (low/high PAR + UV‐B + UV‐A), PA (low/high PAR + UV‐A) or low/high PAR only. While extracellular phlorotannins increased after 10 days, intracellular phlorotannins increased with exposure time and PA and decreased under PAB. Interactive effects of time:radiation wavebands, time:PAR dose as well as radiation wavebands:PAR dose were observed. Low FA contents were detected in the PA and PAB treatments; interactive effects were observed between time:high PAR and PAB:high PAR. Total FA contents were correlated to extra/intracellular phlorotannin contents. Our results suggest that phlorotannins might play a role in intra/extracellular protection by absorption and oxidation processes. Changes in FA content/composition upon UVR and high PAR might be considered as an adaptive mechanism of the A. esculenta juveniles subjected to variations in solar irradiance.
Saproxylic beetle thrives on the openness in management: a case study on the ecological requirements of Cucujus cinnaberinus from Central Europe
Authors: HORÁK JAKUB , CHUMANOVÁ EVA , HILSZCZAŃSKI JACEK
Published: September 2011

Abstract.  1. Saproxylic beetles are a key group when assessing forest biodiversity, and biologists have been trying to explore their ecological requirements.

2. We studied Cucujus cinnaberinus in its recent stronghold (i.e. Czech Republic, Central Europe).

3. Our analyses using a generalised linear model (GLZ) revealed that sufficient sun exposure was the most important habitat parameter at the tree level and that the species preferred dead wood with well‐peeled bark at an intermediate stage of decay at the microhabitat level.

4. Redundancy analysis (RDA) of species associations showed that the microhabitat of C. cinnaberinus was often prepared by early phloeoxylophages. Silvanids and large carabids were significant associates, and the non‐coleopteran taxa associated with C. cinnaberinus were ants (Lasius spp.), mites, springtails, and centipedes. Only one species of bracket fungus Phellinus populicola was significantly associated with C. cinnaberinus.

5. Cucujus cinnaberinus microhabitats were species‐rich compared with those from which this species was absent. C. cinnaberinus shares its habitat with several red‐listed beetles. The most common functional groups were predators and scavengers. However, we found no difference in the composition of functional groups between sites with and without C. cinnaberinus in our study samples.

6. The results contribute to the debate about the decline in saproxylic species in relation to the decline in open spaces in forest landscapes. The habitat requirements of many saproxylic beetles indicate that modern forest management should pay more attention to open forest stands, rather than hands‐off practices that naturally lead to canopy closure.
Variability of Heidelberg Retina Tomograph parameters during exercise
Authors: Saarela Ville , Ahvenvaara Elina , Tuulonen Anja
Published: September 2011

Purpose:  The purpose of this study was to determine whether exercise affects the stereometric parameters representing optic nerve head (ONH) topography.

Methods:  ONH topography, intraocular pressure (IOP) and blood pressure of 30 healthy volunteers were monitored before, during and after dynamic exercise raising systolic blood pressure by a minimum of 30 mmHg. Change in the stereometric ONH parameters was calculated.

Results:  IOP decreased and blood pressure increased during exercise, resulting in an increase in mean ocular perfusion pressure. Exercise was associated with an increase in variance in 17 of the 18 stereometric ONH parameters. The increase in variance was statistically significant in eight parameters, including rim area, cup/disc area ratio and cup shape measure. There was no statistically significant change in image quality. The absolute change from baseline in rim area, cup area, cup/disc area ratio, rim/disc area ratio and rim volume showed a statistically significant (p < 0.05) correlation with change in mean ocular perfusion pressure.

Conclusions:  Exercise increases variability in stereometric ONH parameters. To avoid increased variance in the stereometric parameters, ONH imaging should be performed after allowing sufficient time to rest.
Anti‐hepatitis B surface immunoglobulin reduction in early postoperative period after liver transplantation in hepatitis B virus‐positive patients
Authors: Ishigami Masatoshi , Onishi Yasuharu , Ito Takashi , Katano Yoshiaki , Ito Akihiro , Hirooka Yoshiki , Kiuchi Tetsuya , Goto Hidemi
Published: September 2011

Aim:  We investigated a protocol that lowered the necessary dose of anti‐hepatitis B surface immunoglobulin (HBIg) with frequent monitoring of hepatitis B surface antigen (HBsAg) and antibody (HBsAb) levels in the early post‐transplant period.

Methods:  Fifteen hepatitis B virus (HBV)‐positive patients were studied. We administered a nucleoside analog from the preoperative period, high dose HBIg was used intraoperatively (200 IU/kg in the patients who weighed less than 50 kg, and 10 000 IU in those who weighed more than or equal to 50 kg) and was continued every day (5000–10 000 IU/day). Thereafter, HBIg was administered to keep the target trough titers. We evaluated the effectiveness and safety of this protocol for preventing HBV reactivation.

Results:  The average use of HBIg during the first three postoperative months (POM) was 27.9 ± 9.6 Kilo International Units. The average cost was $US11 800 in the first three postoperative months, compared with other previously reported protocols (about $20 000–40 000). HBV reactivation was detected in only one patient (6.7%) during the median follow up of 64 months (range: 12–86 months).

Conclusions:  The present protocol for HBIg administration, which used frequent monitoring of HBsAg and HBsAb levels to determine the minimum required dose, was both safe and effective, and contributed to overall cost saving after liver transplantation.
Numerical modeling of oblique hypervelocity impacts on strong ductile targets
Authors: DAVISON Thomas M. , COLLINS Gareth S. , ELBESHAUSEN Dirk , WÜNNEMANN Kai , KEARSLEY Anton
Published: September 2011

Abstract– The majority of meteorite impacts occur at oblique incidence angles. However, many of the effects of obliquity on impact crater size and morphology are poorly understood. Laboratory experiments and numerical models have shown that crater size decreases with impact angle, the along‐range crater profile becomes asymmetric at low incidence angles, and below a certain threshold angle the crater planform becomes elliptical. Experimental results at approximately constant impact velocity suggest that the elliptical threshold angle depends on target material properties. Herein, we test the hypothesis that the threshold for oblique crater asymmetry depends on target material strength. Three‐dimensional numerical modeling offers a unique opportunity to study the individual effects of both impact angle and target strength; however, a systematic study of these two parameters has not previously been performed. In this work, the three‐dimensional shock physics code iSALE‐3D is validated against laboratory experiments of impacts into a strong, ductile target material. Digital elevation models of craters formed in laboratory experiments were created from stereo pairs of scanning electron microscope images, allowing the size and morphology to be directly compared with the iSALE‐3D craters. The simulated craters show excellent agreement with both the crater size and morphology of the laboratory experiments. iSALE‐3D is also used to investigate the effect of target strength on oblique incidence impact cratering. We find that the elliptical threshold angle decreases with decreasing target strength, and hence with increasing cratering efficiency. Our simulations of impacts on ductile targets also support the prediction from Chapman and McKinnon (1986) that cratering efficiency depends on only the vertical component of the velocity vector.
Very low strengths of interplanetary meteoroids and small asteroids
Authors: POPOVA Olga , BOROVIČKA Jiří , HARTMANN William K. , SPURNÝ Pavel , GNOS Edwin , NEMTCHINOV Ivan , TRIGO‐RODRÍGUEZ Josep M.
Published: September 2011

Abstract– We have assembled data on 13 cases of meteorite falls with accurate tracking data on atmospheric passage. In all cases, we estimate the bulk strength of the object corresponding to its earliest observed or inferred fragmentation in the high atmosphere, and can compare these values with measured strengths of meteorites in the taxonomic class for that fall. In all 13 cases, the strength corresponding to earliest observed or inferred fragmentation is much less than the compressive or tensile strength reported for that class of stony meteorites. Bulk strengths upon atmospheric entry of these bodies are shown to be very low, 0.1 to approximately 1 MPa on first breakup, and maximal strength on breakup as 1–10 MPa corresponding to weak and “crumbly” objects, whereas measured average tensile strength of the similar meteorite classes is about 30 MPa. We find a more random relation between bulk sample strength and sample mass than is suggested by a commonly used empirical power law. We estimate bulk strengths on entry being characteristically of the order of 10−1–10−2 times the tensile strengths of recovered samples. We conclude that pre‐entry, meter‐scale interplanetary meteoroids are typically highly fractured or in some cases rubbly in texture, presumably as a result of their parent bodies’ collisional history, and can break up under stresses of a few megapascals. The weakness of some carbonaceous objects may result from very porous primordial accretional structures, more than fractures. These conclusions have implications for future asteroid missions, sample extraction, and asteroid hazard mitigation.
smatr 3– an R package for estimation and inference about allometric lines
Authors: Warton David I. , Duursma Remko A. , Falster Daniel S. , Taskinen Sara
Published: September 2011

1. The Standardised Major Axis Tests and Routines (SMATR) software provides tools for estimation and inference about allometric lines, currently widely used in ecology and evolution.

2. This paper describes some significant improvements to the functionality of the package, now available on R in smatr version 3.

3. New inclusions in the package include sma and ma functions that accept formula input and perform the key inference tasks; multiple comparisons; graphical methods for visualising data and checking (S)MA assumptions; robust (S)MA estimation and inference tools.
How to fit nonlinear plant growth models and calculate growth rates: an update for ecologists
Authors: Paine C. E. Timothy , Marthews Toby R. , Vogt Deborah R. , Purves Drew , Rees Mark , Hector Andy , Turnbull Lindsay A.
Published: September 2011

1. Plant growth is a fundamental ecological process, integrating across scales from physiology to community dynamics and ecosystem properties. Recent improvements in plant growth modelling have allowed deeper understanding and more accurate predictions for a wide range of ecological issues, including competition among plants, plant–herbivore interactions and ecosystem functioning.

2. One challenge in modelling plant growth is that, for a variety of reasons, relative growth rate (RGR) almost universally decreases with increasing size, although traditional calculations assume that RGR is constant. Nonlinear growth models are flexible enough to account for varying growth rates.

3. We demonstrate a variety of nonlinear models that are appropriate for modelling plant growth and, for each, show how to calculate function‐derived growth rates, which allow unbiased comparisons among species at a common time or size. We show how to propagate uncertainty in estimated parameters to express uncertainty in growth rates. Fitting nonlinear models can be challenging, so we present extensive worked examples and practical recommendations, all implemented in R.

4. The use of nonlinear models coupled with function‐derived growth rates can facilitate the testing of novel hypotheses in population and community ecology. For example, the use of such techniques has allowed better understanding of the components of RGR, the costs of rapid growth and the linkage between host and parasite growth rates. We hope this contribution will demystify nonlinear modelling and persuade more ecologists to use these techniques.
Auto-calibration Based Control and Its Application to a Kind of Electrohydraulic Poppet Valves
Authors: Opdenbosch Patrick , Sadegh Nader , Book Wayne
Published: September 2011

This paper describes a novel learning/adaptive state trajectory control method and its application to electronic hydraulic pressure control. The control algorithm presented herein learns the inverse input-state mapping of the plant at the same time this map is employed in the feedforward loop to force the state of the plant to asymptotically converge to a prescribed state trajectory. The algorithm accomplishes this task without requiring prior exact information about the state transition map of the plant. The novel controller is applied to an electrohydraulic poppet valve with the objective of tracking a desired supply pressure signal. In this application, the controller learns the inverse conductance characteristics of the valve. The supply pressure tracking performance subject to the proposed controller is validated through experimental data.
Model-Based Control of the Air Fuel Ratio for Gasoline Direct Injection Engines via Advanced Co-Simulation: An Approach to Reduce the Development Cycle of Engine Control Systems
Authors: Gaeta Alessandro di , Montanaro Umberto , Giglio Veniero
Published: September 2011

Nowadays, the precise control of the air fuel ratio (AFR) in spark ignition (SI) engines plays a crucial role in meeting the more and more restrictive standard emissions for the passenger cars and the fuel economy required by the automotive market as well. To attain this demanding goal, the development of an advanced AFR control strategy embedding highly predictive models becomes mandatory for the next generation of electronic control unit (ECU). Conversely, the adoption of more complex control strategies affects the development time of the ECU increasing the time-to-market of new engine models. In this paper to solve the AFR control problem for gasoline direct injection (GDI) and to speed up the design of the entire control system, a gain scheduling PI model-based control strategy is proposed. To this aim, AFR dynamics are modeled via a first order time delay system whose parameters vary strongly with the fresh air mass entering the cylinders. Nonlinear relations have been found to describe the behavior of model parameters in function of air mass. Closed loop performances, when this novel controller is nested in the control loop, are compared to those provided by the classical PI Ziegler–Nichols control action with respect to different cost functions. Model validation as well as the effectiveness of the control design are carried out by means of ECU-1D engine co-simulation environment for a wide range of engine working conditions. The combination in one integrated designing environment of control systems and virtual engine, simulated through high predictive commercial one dimensional code, becomes a high predictive tool for automotive control engineers and enables fast prototyping.
Modeling of charging effect on ion induced secondary electron emission from nanostructured materials
Authors: Ohya Kaoru , Takami Daiki , Yamanaka Takuya
Published: September 2011

Charging effects caused by secondary electron (SE) emission of a nanostructured material during ion beam irradiation are investigated by simulation. The materials simulated are a 100-nm-high SiO2 step on an Si substrate, and a 100-nm-deep trench through an SiO2 film to the Si substrate. Each position on the surface is irradiated with a 30 keV Ga ion beam. A Monte Carlo based model for SE emission from SiO2 and Si is used for simulation in which the charging of SiO2 induced by ion beam irradiation is taken into account. Dynamic and self-consistent calculations are performed to model the transport of the ions and SEs, the charge accumulation in SiO2, and the electric field in the SiO2 and in the vacuum. The calculated charging characteristics are compared with those calculated for a 1 keV electron beam. For Ga ion incidence; as a result of successive positive charging, the SE yield of the SiO2 layer decreases more strongly than for electron incidence, eventually vanishing, and the surface voltage progressively increases. The SE yield increases when the Ga ion incidence occurs at the position near the step edge on the layer, in a similar way to that observed for the electron incidence. The increase in the yield is more localized than for electron incidence. When the trench is irradiated with the Ga ion beam, the sidewall of the trench becomes negatively charged from reentrance of SEs emitted from the bottom of the trench. This negative charging increases the SE yield at the bottom of the trench (an effect also observed in the simulations of electron beam irradiation), because it assists SEs, which may be reabsorbed by the sidewall if they are not charged, to exit the trench. As the width of the trench decreases, the increase in the electron yield is enhanced. This enhancement is stronger for the incident ion beam than for the electron beam.
Three-Dimensional Correlation of Steric and Electronic Free Energy Relationships Guides Asymmetric Propargylation
Authors: Harper Kaid C. , Sigman Matthew S.
Published: September 2011

An unexpected synergy between a ligand's
steric bulk and its electronic structure improves a stereoselective catalyst.
Rescuing Wolves from Politics: Wildlife as a Public Trust Resource
Authors: Bruskotter Jeremy T. , Enzler Sherry A. , Treves Adrian
Published: September 2011

Long-term conservation of gray wolves is possible if states recognize a legal obligation to conserve species as a public trust resource.
Response to Comment on “The Response of Vegetation on the Andean Flank in Western Amazonia to Pleistocene Climate Change”
Authors: Cárdenas Macarena L. , Gosling William D. , Sherlock Sarah C. , Poole Imogen , Pennington R. Toby , Mothes Patricia
Published: September 2011

Puyasena
et al
. question our interpretation of climate-driven vegetation change on the Andean flank in western Amazonia during the middle Pleistocene and suggest that the use of
Podocarpus
spp. as a proxy of past climate change should be reassessed. We defend our assertion that vegetation change at the Erazo study site was predominantly driven by climate change due to concomitant changes recorded by multiple taxa in the fossil record.
Evidence of Water Vapor in Excess of Saturation in the Atmosphere of Mars
Authors: Maltagliati L. , Montmessin F. , Fedorova A. , Korablev O. , Forget F. , Bertaux J.-L.
Published: September 2011

Spacecraft observations reveal more water vapor in the atmosphere of Mars than would be expected if vapor pressure controlled the water vapor profile.
The Global Magnetic Field of Mercury from MESSENGER Orbital Observations
Authors: Anderson Brian J. , Johnson Catherine L. , Korth Haje , Purucker Michael E. , Winslow Reka M. , Slavin James A. , Solomon Sean C. , McNutt Ralph L. , Raines Jim M. , Zurbuchen Thomas H.
Published: September 2011

Displacement of Mercury's magnetic dipole implies that the surface field has a north-south asymmetry.
Hollows on Mercury: MESSENGER Evidence for Geologically Recent Volatile-Related Activity
Authors: Blewett David T. , Chabot Nancy L. , Denevi Brett W. , Ernst Carolyn M. , Head James W. , Izenberg Noam R. , Murchie Scott L. , Solomon Sean C. , Nittler Larry R. , McCoy Timothy J. , Xiao Zhiyong , Baker David M. H. , Fassett Caleb I. , Braden Sarah E. , Oberst Jürgen , Scholten Frank , Preusker Frank , Hurwitz Debra M.
Published: September 2011

Rimless shallow depressions on Mercury may still be forming by outgassing, volcanism, sublimation, or space weathering.
Predicting the Flow of Real Polymers
Authors: Larson Ronald G.
Published: September 2011

A new model can account for the flow properties of molten polymers that contain mixtures of branched molecules with different sizes and shapes.
Sunshine on a Cloudy Forecast
Authors: Heavens Nicholas G.
Published: September 2011

The observation of supersaturated layers in Mars' atmosphere has implications for modeling the dynamics of its climate and water cycle.
Turkey and Science Academies
Authors: Alberts Bruce
Published: September 2011

The government of Turkey recently announced that it will henceforth appoint the president of the Turkish Academy of Sciences (TÜBA) and also, directly or indirectly, appoint the majority of academy members. In response, TÜBA's members have threatened to resign and establish a new academy that is independent of the government. What happens next could dramatically affect Turkey's future, both because strong merit-based research in science and technology is a critical driver of modern economies, and because Turkey—like all other nations—will need to support and retain its native talent in order to prosper in the highly competitive world of the 21st century.
Experts Debate Polypill: A Single Pill for Global Health
Authors: Reardon Sara
Published: September 2011

Advocates say a "polypill" combining several cheap, well-tested heart drugs could supplement exercise and a healthy diet in preventing heart disease, but many cardiologists are sharply critical of the potential risks.
Playing by Ear
Authors: Reardon Sara
Published: September 2011

Audio-based computer games are helping blind volunteers learn navigation skills and may unlock mysteries of the sightless mind.
First Global Telescope Opens an Eye on the Cold Universe
Authors: Normile Dennis , Clery Daniel
Published: September 2011

Within days, astronomers will start peering into the coolest corners of the cosmos using a partially completed array of antennas in the deserts of northern Chile.
Colorimetric Nucleic Acid Testing Assay for RNA Virus Detection Based on Circle-to-Circle Amplification of Padlock Probes
Authors: Ke Rongqin , Zorzet Anna , Göransson Jenny , Lindegren Gunnel , Sharifi-Mood Batool , Chinikar Sadegh , Mardani Masoud , Mirazimi Ali , Nilsson Mats
Published: September 2011

We developed a molecular diagnostic method for detection of RNA virus based on padlock probes and colorimetric readout. The feasibility of our approach was demonstrated by using detection of Crimean-Congo hemorrhagic fever (CCHF) virus as a model. Compared with conventional PCR-based methods, our approach does not require advanced equipment, involves easier assay design, and has a sensitivity of 10
3
viral copies/ml. By using a cocktail of padlock probes, synthetic templates representing different viral strain variants could be detected. We analyzed 34 CCHF patient samples, and all patients were correctly diagnosed when the results were compared to those of the current real-time PCR method. This is the first time that highly specific padlock probes have been applied to detection of a highly variable target sequence typical of RNA viruses.
Impact of Genomic Sequence Variability on Quantitative PCR Assays for Diagnosis of Polyomavirus BK Infection
Authors: Randhawa P. , Kant J. , Shapiro R. , Tan H. , Basu A. , Luo C.
Published: September 2011

Knowledge of polyomavirus BK (BKV) genomic diversity has greatly expanded. The implications of BKV DNA sequence variation for the performance of molecular diagnostic assays is not well studied. We analyzed 184 publically available VP-1 sequences encompassing the BKV genomic region targeted by an in-house quantitative hydrolysis probe-based PCR assay. A perfect match with the PCR primers and probe was seen in 81 sequences. One Dun and 13 variant prototype oligonucleotides were synthesized as artificial targets to determine how they affected the performance of PCR. The sensitivity of detection of BKV in the PCR assay was a function of the viral genotype. Prototype 1 (BKV Dun) could be reliably detected at concentrations as low as 10 copies/μl. However, consistent detection of all BKV variants was possible only at concentrations of 10,000 copies/μl or higher. For BKV prototypes with 2 or more mismatches (representing genotype IV, genotype II, and genotype 1c strains), the calculated viral loads were 0.57 to 3.26% of the expected values. In conclusion, variant BKV strains lower the sensitivity of detection and may have a substantial effect on quantitation of the viral load. Physicians need to be cognizant of these effects when interpreting the results of quantitative PCR testing in transplant recipients, particularly if there is a discrepancy between the clinical impression and the measured viral load.
Dermatophyte Identification Using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Theel Elitza S. , Hall Leslie , Mandrekar Jayawant , Wengenack Nancy L.
Published: September 2011

The performance of the Bruker Biotyper matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometer (MS) for the identification of dermatophytes from clinical cultures was compared to that of dermatophyte identification using 28S rRNA gene sequencing. The MALDI Biotyper library (MBL; version 3.0) was used alone and in combination with a supplemented library containing an additional 20 dermatophyte spectra (S-MBL). Acquired spectra were interpreted using both the manufacturer-recommended scores (genus, ≥1.7; species, ≥2.0) and adjusted cutoff values established by this study (genus, ≥1.5; species, ≥1.7); identifications required a minimum 10% difference in scores between the top two different organisms to be considered correct. One hundred well-characterized, archived dermatophyte isolates and 71 fresh dermatophyte cultures were evaluated using both libraries and both sets of cutoff criteria. Collectively, the S-MBL significantly outperformed the MBL at both the genus (93% versus 37.4%;
P
< 0,0001) and species (59.6% versus 20.5%;
P
< 0.0001) levels when using the adjusted score criteria. Importantly, application of the lowered cutoff values significantly improved genus (
P
= 0.005)- and species (
P
< 0.0001)-level identification for the S-MBL, without leading to an increase in misidentifications. MALDI-TOF MS is a cost-effective and rapid alternative to traditional or molecular methods for dermatophyte identification, provided that the reference library is supplemented to sufficiently encompass clinically relevant, intraspecies strain diversity.
Identification of a Cullin5-ElonginB-ElonginC E3 Complex in Degradation of Feline Immunodeficiency Virus Vif-Mediated Feline APOBEC3 Proteins
Authors: Wang Jiawen , Zhang Wenyan , Lv Mingyu , Zuo Tao , Kong Wei , Yu Xianghui
Published: September 2011

Various feline APOBEC3 (fA3) proteins exhibit broad antiviral activities against a wide range of viruses, such as feline immunodeficiency virus (FIV), feline foamy virus (FFV), and feline leukemia virus (FeLV), as well as those of other species. This activity can be counteracted by the FIV Vif protein, but the mechanism by which FIV Vif suppresses fA3s is unknown. In the present study, we demonstrated that FIV Vif could act via a proteasome-dependent pathway to overcome fA3s. FIV Vif interacted with feline cellular proteins Cullin5 (Cul5), ElonginB, and ElonginC to form an E3 complex to induce degradation of fA3s. Both the dominant-negative Cul5 mutant and a C-terminal hydrophilic replacement ElonginC mutant potently disrupted the FIV Vif activity against fA3s. Furthermore, we identified a BC-box motif in FIV Vif that was essential for the recruitment of E3 ubiquitin ligase and also required for FIV Vif-mediated degradation of fA3s. Moreover, despite the lack of either a Cul5-box or a HCCH zinc-binding motif, FIV Vif specifically selected Cul5. Therefore, FIV Vif may interact with Cul5 via a novel mechanism. These finding imply that SOCS proteins may possess distinct mechanisms to bind Cul5 during formation of the Elongin-Cullin-SOCS box complex.
RNA-Based Immunity Terminates Viral Infection in Adult Drosophila in the Absence of Viral Suppression of RNA Interference: Characterization of Viral Small Interfering RNA Populations in Wild-Type and Mutant Flies
Authors: Han Yan-Hong , Luo Ying-Jun , Wu Qingfa , Jovel Juan , Wang Xiao-Hong , Aliyari Roghiyh , Han Chenggui , Li Wan-Xiang , Ding Shou-Wei
Published: September 2011

Replication of viral RNA genomes in fruit flies and mosquitoes induces the production of virus-derived small interfering RNAs (siRNAs) to specifically reduce virus accumulation by RNA interference (RNAi). However, it is unknown whether the RNA-based antiviral immunity (RVI) is sufficiently potent to terminate infection in adult insects as occurs in cell culture. We show here that, in contrast to robust infection by Flock house virus (FHV), infection with an FHV mutant (FHVΔB2) unable to express its RNAi suppressor protein B2 was rapidly terminated in adult flies. FHVΔB2 replicated to high levels and induced high mortality rates in
dicer-2
and
argonaute-2
mutant flies that are RNAi defective, demonstrating that successful infection of adult
Drosophila
requires a virus-encoded activity to suppress RVI.
Drosophila
RVI may depend on the RNAi activity of viral siRNAs since efficient FHVΔB2 infection occurred in
argonaute-2
and
r2d2
mutant flies despite massive production of viral siRNAs. However, RVI appears to be insensitive to the relative abundance of viral siRNAs since FHVΔB2 infection was terminated in flies carrying a partial loss-of-function mutation in
loquacious
required for viral siRNA biogenesis. Deep sequencing revealed a low-abundance population of Dicer-2-dependent viral siRNAs accompanying FHVΔB2 infection arrest in RVI-competent flies that included an approximately equal ratio of positive and negative strands. Surprisingly, viral small RNAs became strongly biased for positive strands at later stages of infection in RVI-compromised flies due to genetic or viral suppression of RNAi. We propose that degradation of the asymmetrically produced viral positive-strand RNAs associated with abundant virus accumulation contributes to the positive-strand bias of viral small RNAs.
Adenovirus with Hexon Tat-Protein Transduction Domain Modification Exhibits Increased Therapeutic Effect in Experimental Neuroblastoma and Neuroendocrine Tumors
Authors: Yu Di , Jin Chuan , Leja Justyna , Majdalani Nadim , Nilsson Berith , Eriksson Fredrik , Essand Magnus
Published: September 2011

Adenovirus serotype 5 (Ad5) is widely used as an oncolytic agent for cancer therapy. However, its infectivity is highly dependent on the expression level of coxsackievirus-adenovirus receptor (CAR) on the surfaces of tumor cells. Furthermore, infected cells overproduce adenovirus fiber proteins, which are released prior to cell lysis. The released fibers block CAR on noninfected neighboring cells, thereby preventing progeny virus entry. Our aim was to add a CAR-independent infection route to Ad5 to increase the infectivity of tumor cells with low CAR expression and prevent the fiber-masking problem. We constructed Ad5 viruses that encode the protein transduction domain (PTD) of the HIV-1 Tat protein (Tat-PTD) in hypervariable region 5 (HVR5) of the hexon protein. Tat-PTD functions as a cell-penetrating peptide, and Tat-PTD-modified Ad5 showed a dramatic increased transduction of CAR-negative cell lines compared to unmodified vector. Moreover, while tumor cell infectivity was severely reduced for Ad5 in the presence of fiber proteins, it was only marginally reduced for Tat-PTD-modified Ad5. Furthermore, because of the sequence alteration in the hexon HVR, coagulation factor X-mediated virus uptake was significantly reduced. Mice harboring human neuroblastoma and neuroendocrine tumors show suppressed tumor growths and prolonged survival when treated with Tat-PTD-modified oncolytic viruses. Our data suggest that modification of Ad5 with Tat-PTD in HVR5 expands its utility as an oncolytic agent.
Inhibitory Effects of Bile Acids and Synthetic Farnesoid X Receptor Agonists on Rotavirus Replication
Authors: Kim Yunjeong , Chang Kyeong-Ok
Published: September 2011

Rotaviruses (group A rotaviruses) are the most important cause of severe gastroenteritis in infants and children worldwide. Currently, an antiviral drug is not available and information on therapeutic targets for antiviral development is limited for rotavirus infection. Previously, it was shown that lipid homeostasis is important in rotavirus replication. Since farnesoid X receptor (FXR) and its natural ligands bile acids (such as chenodeoxycholic acid [CDCA]) play major roles in cholesterol and lipid homeostasis, we examined the effects of bile acids and synthetic FXR agonists on rotavirus replication in association with cellular lipid levels. In a mouse model of rotavirus infection, effects of oral administration of CDCA on fecal rotavirus shedding were investigated. The results demonstrate the following. First, the intracellular contents of triglycerides were significantly increased by rotavirus infection. Second, CDCA, deoxycholic acid (DCA), and other synthetic FXR agonists, such as GW4064, significantly reduced rotavirus replication in cell culture in a dose-dependent manner. The reduction of virus replication correlated positively with activation of the FXR pathway and reduction of cellular triglyceride contents (r2= 0.95). Third, oral administration of CDCA significantly reduced fecal virus shedding in mice (P< 0.05). We conclude that bile acids and FXR agonists play important roles in the suppression of rotavirus replication. The inhibition mechanism is proposed to be the downregulation of lipid synthesis induced by rotavirus infection.
Kaposi's Sarcoma-Associated Herpesvirus Noncoding Polyadenylated Nuclear RNA Interacts with Virus- and Host Cell-Encoded Proteins and Suppresses Expression of Genes Involved in Immune Modulation
Authors: Rossetto Cyprian C. , Pari Gregory S.
Published: September 2011

During lytic infection, Kaposi's sarcoma-associated herpesvirus (KSHV) expresses a polyadenylated nuclear RNA (PAN RNA). This noncoding RNA (ncRNA) is localized to the nucleus and is the most abundant viral RNA during lytic infection; however, to date, the role of PAN RNA in the virus life cycle is unknown. Many examples exist where ncRNAs have a defined key regulatory function controlling gene expression by various mechanisms. Our goal for this study was to identify putative binding partners for PAN RNA in an effort to elucidate a possible function for the transcript in KSHV infection. We employed an
in vitro
affinity protocol where PAN RNA was used as bait for factors present in BCBL-1 cell nuclear extract to show that PAN RNA interacts with several virus- and host cell-encoded factors, including histones H1 and H2A, mitochondrial and cellular single-stranded binding proteins (SSBPs), and interferon regulatory factor 4 (IRF4). RNA chromatin immunoprecipitation (ChIP) assays confirmed that PAN RNA interacted with these factors in the infected cell environment. A luciferase reporter assay showed that PAN RNA expression interfered with the ability of IRF4/PU.1 to activate the interleukin-4 (IL-4) promoter, strongly suggesting a role for PAN RNA in immune modulation. Since the proteomic screen and functional data suggested a role in immune responses, we investigated if constitutive PAN RNA expression could affect other genes involved in immune responses. PAN RNA expression decreased expression of gamma interferon, interleukin-18, alpha interferon 16, and RNase L. These data strongly suggest that PAN RNA interacts with viral and cellular proteins and can function as an immune modulator.
Autophagy Required for Hepatitis B Virus Replication in Transgenic Mice
Authors: Tian Yongjun , Sir Donna , Kuo Cheng-fu , Ann David K. , Ou Jing-hsiung James
Published: September 2011

Recent studies indicate that hepatitis B virus (HBV) may induce autophagy to enhance its replication in cell cultures. To understand whether autophagy can indeed enhance HBV replication
in vivo
, we generated HBV transgenic mice with liver-specific knockout of the Atg5 gene, a gene critical for the initiation of autophagy. Immunoblot analyses confirmed the inhibition of autophagy in the livers of Atg5 knockout mice. This inhibition of autophagy slightly reduced HBV gene expression and affected nuclear localization of the HBV core protein. It also reduced the HBV DNA level in sera by more than 90% and the level of the HBV DNA replicative intermediate in the mouse liver to an almost undetectable level. Our results thus demonstrate that autophagy is important for HBV replication
in vivo
and raise the possibility of targeting this pathway to treat HBV patients.
Communicating the risk of injury in schoolboy rugby: using Poisson probability as an alternative presentation of the epidemiology
Authors: Parekh Nikesh , Hodges Stewart D , Pollock Allyson M , Kirkwood Graham
Published: September 2011

Background

The communication of injury risk in rugby and other sports is underdeveloped and parents, children and coaches need to be better informed about risk.

Method

A Poisson distribution was used to transform population based incidence of injury into average probabilities of injury to individual players.

Results

The incidence of injury in schoolboy rugby matches range from 7 to 129.8 injuries per 1000 player-hours; these rates translate to average probabilities of injury to a player of between 12% and 90% over a season.

Conclusion

Incidence of injury and average probabilities of injury over a season should be published together in all future epidemiological studies on school rugby and other sports. More research is required on informing and communicating injury risks to parents, staff and children and how it affects monitoring, decision making and prevention strategies.
Enhancement of antibiotic susceptibility ofStenotrophomonas maltophiliausing a polyclonal antibody developed against an ABC multidrug efflux pump
Authors: Al-Hamad Arif , Burnie James , Upton Mathew
Published: September 2011

Stenotrophomonas maltophilia is an emerging nosocomial pathogen capable of causing healthcare-associated infections, including pneumonia and bacteremia. Intrinsic resistance in S. maltophilia is exhibited towards many broad-spectrum antibiotics, and treatment recommendations are controversial. One of the major causes of antimicrobial resistance is attributed to a robust array of efflux pumps that extrude drug compounds from the cell. Using checkerboard and growth kinetic assays, we evaluated the in vitro activity of a polyclonal antibody raised against an ATP-binding cassette efflux protein in S. maltophilia. Six clinical strains of S. maltophilia and one type strain were challenged with co-trimoxazole, ticarcillin–clavulanate, and ciprofloxacin, alone and in combination with antibody. One clinical strain was tested by growth curve experiments for each antibiotic–antibody combination. The use of antibody resulted in significantly increased susceptibility in 71.4% (15/21) of treatments tested, with 33.3% displaying synergy and 38.1% an additive effect. In growth kinetic studies, synergy was obtained for each antibiotic–antibody combination. Thus, the use of antibody raised against multidrug efflux pumps for the treatment of multidrug-resistant organisms warrants further investigation. Antibody targeting substrate recognition sites, or other functionally important epitopes, may lead to inhibition of multiple efflux pumps that share the same substrate and is an attractive area that should be explored.
ICP-SFMS SEARCH FOR LONG-LIVED NATURALLY-OCCURRING HEAVY, SUPERHEAVY AND SUPERACTINIDE NUCLEI COMPARED TO AMS EXPERIMENTS
Authors: MARINOV A. , PAPE A. , KASHIV Y. , KOLB D. , HALICZ L. , SEGAL I. , BRANDT R.
Published: September 2011

Negative results obtained in AMS searches by Dellinger et al. on mostly unrefined ores have led them to conclude that the very heavy long-lived species found in chemically processed samples with ICP-SFMS by Marinov et al. are artifacts. We argue that it may not be surprising that results obtained from small random samplings of inhomogeneous natural minerals would contrast with concentrations found in homogeneous materials extracted from large quantities of ore. We also point out that it is possible that the groups of counts at masses 296 and 294 seen by Dellinger et al. could be, within experimental uncertainties, due to 296 Rg and 294 eka-Bi in long-lived isomeric states. In such case, the experiments of Dellinger et al. lend support to the experiments of Marinov et al.
NHLBI-AbDesigner: an online tool for design of peptide-directed antibodies
Authors: Pisitkun Trairak , Hoffert Jason D. , Saeed Fahad , Knepper Mark A.
Published: September 2011

Investigation of physiological mechanisms at a cellular level often requires production of high-quality antibodies, frequently using synthetic peptides as immunogens. Here we describe a new, web-based software tool called NHLBI- AbDesigner that allows the user to visualize the information needed to choose optimal peptide sequences for peptide-directed antibody production ( http://helixweb.nih.gov/AbDesigner/ ). The choice of an immunizing peptide is generally based on a need to optimize immunogenicity, antibody specificity, multispecies conservation, and robustness in the face of posttranslational modifications (PTMs). AbDesigner displays information relevant to these criteria as follows: 1) “Immunogenicity Score,” based on hydropathy and secondary structure prediction; 2) “Uniqueness Score,” a predictor of specificity of an antibody against all proteins expressed in the same species; 3) “Conservation Score,” a predictor of ability of the antibody to recognize orthologs in other animal species; and 4) “Protein Features” that show structural domains, variable regions, and annotated PTMs that may affect antibody performance. AbDesigner displays the information online in an interactive graphical user interface, which allows the user to recognize the trade-offs that exist for alternative synthetic peptide choices and to choose the one that is best for a proposed application. Several examples of the use of AbDesigner for the display of such trade-offs are presented, including production of a new antibody to Slc9a3. We also used the program in large-scale mode to create a database listing the 15-amino acid peptides with the highest Immunogenicity Scores for all known proteins in five animal species, one plant species ( Arabidopsis thaliana), and Saccharomyces cerevisiae.
Rate of fall in blood glucose and recurrent hypoglycemia affect glucose dynamics and noradrenergic activation in the ventromedial hypothalamus
Authors: Barnes Meredith B. , Lawson Marcus A. , Beverly J. Lee
Published: September 2011

Noradrenergic activity in the ventromedial hypothalamus (VMH) is increased and activates a sympathoadrenal response during hypoglycemia. How the rate at which hypoglycemia develops affects local glucose concentrations and norepinephrine (NE) release was evaluated by placing microdialysis probes into the VMH of male Sprague-Dawley rats receiving insulin (20 mU·kg−1·min−1) and variable glucose infusions. During a first episode of hypoglycemia, interstitial glucose concentrations in the VMH generally declined at the same rate as plasma glucose; however, the faster hypoglycemia developed, the greater the magnitude of the initial NE release in the VMH ( r2 = 0.72, P < 0.001). Following recurrent episodes of hypoglycemia, VMH glucose decreased at a slower rate than plasma glucose, and the initial NE release was attenuated at the same rates of blood glucose decline. The plasma glucose threshold for the initial NE release in VMH was similar for all groups (∼3.23 mM); however, the VMH glucose threshold was stimulated and was lower when blood glucose declined more slowly (0.86 ± 0.06 vs. 1.06 ± 0.04 mmol/l, P < 0.01). The timing of the initial increase in NE release in VMH corresponded with an increase in plasma epinephrine during the first episode of hypoglycemia but not following recurrent hypoglycemia. Although a decrease in VMH glucose concentration is required for noradrenergic activation in VMH, there does not appear to be a set glucose threshold within the VMH for activation of this response.